Potent neutralizing antibodies against sars-cov-2, generation and uses thereof

ABSTRACT

The subject matter described herein relates to potent monoclonal and bispecific antibodies capable of neutralizing a SARS-CoV-2 viruses and methods of generating the antibodies.

This application claims the benefit of and priority to U.S. ProvisionalPatent Application No. 63/027,935, filed on May 20, 2020, U.S.Provisional Patent Application No. 63/032,518, filed on May 29, 2020,U.S. Provisional Patent Application No. 63/039,977, filed on Jun. 16,2020, U.S. Provisional Patent Application No. 63/063,106, filed Aug. 7,2020, U.S. Provisional Patent Application No. 63/123,767, filed Dec. 10,2020, U.S. Provisional Patent Application No. 63/060,116, filed on Aug.2, 2020, U.S. Provisional Patent Application No. 63/117,908, filed onNov. 24, 2020, and U.S. Provisional Patent Application No. 63/165,729,filed on Mar. 24, 2021, the contents of each of which is herebyincorporated by reference in its entirety.

All patents, patent applications and publications cited herein arehereby incorporated by reference in their entirety. The disclosures ofthese publications in their entireties are hereby incorporated byreference into this application.

This patent disclosure contains material that is subject to copyrightprotection. The copyright owner has no objection to the facsimilereproduction by anyone of the patent document or the patent disclosureas it appears in the U.S. Patent and Trademark Office patent file orrecords, but otherwise reserves any and all copyright rights.

BACKGROUND OF THE INVENTION

Coronavirus disease 2019 (COVID-19) is an infectious disease caused bythe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thedisease affects multiple organs in the body including the lungs. Thereis an urgent need for the development of therapeutics to combatCOVID-19.

SUMMARY OF THE INVENTION

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3of SEQ ID NO: 63. In some embodiments, the variable domain of the firstlight chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1,CDR2, and CDR3 of SEQ ID NO: 64. In some embodiments, the variabledomain of the second heavy chain comprises CDR1, CDR2, and CDR3 of SEQID NO: 61 or CDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments,the variable domain of the second light chain comprises CDR1, CDR2, andCDR3 SEQ ID NO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on an S protein of aSARS-CoV-2 particle.

In certain aspects, the invention provides a method of treating aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a composition comprising a bispecificmolecule, wherein the bispecific molecule comprises a first polypeptidechain and a second polypeptide chain, wherein: the first polypeptidechain comprises: a first light chain comprising a variable domain and aconstant domain; a first heavy chain comprising a variable domain and aconstant domain; the second polypeptide chain comprises: a second lightchain comprising a variable domain and a constant domain; and a secondheavy chain comprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66. In someembodiments, the variable domain of the first heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3 of SEQ IDNO: 63. In some embodiments, the variable domain of the first lightchain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1, CDR2, andCDR3 of SEQ ID NO: 64. In some embodiments, the variable domain of thesecond heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 61 orCDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments, the variabledomain of the second light chain comprises CDR1, CDR2, and CDR3 SEQ IDNO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a method of preventing aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a composition comprising a bispecificmolecule, wherein the bispecific molecule comprises a first polypeptidechain and a second polypeptide chain, wherein: the first polypeptidechain comprises: a first light chain comprising a variable domain and aconstant domain; a first heavy chain comprising a variable domain and aconstant domain; the second polypeptide chain comprises: a second lightchain comprising a variable domain and a constant domain; and a secondheavy chain comprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3of SEQ ID NO: 63. In some embodiments, the variable domain of the firstlight chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1,CDR2, and CDR3 of SEQ ID NO: 64. In some embodiments, the variabledomain of the second heavy chain comprises CDR1, CDR2, and CDR3 of SEQID NO: 61 or CDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments,the variable domain of the second light chain comprises CDR1, CDR2, andCDR3 SEQ ID NO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of asynthesized monoclonal antibody, or a functional fragment thereof,comprising a heavy chain having a variable domain and a constant domainand a light chain having a variable domain and a constant domain,wherein the antibody binds an antigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody neutralizes a coronavirus. In some embodiments, the coronavirusis SARS-CoV-2. In some embodiments, the antibody specifically binds anepitope on the surface of the coronavirus. In some embodiments, theepitope comprises at least a portion of a coronavirus spike protein. Insome embodiments, the at least a portion of a coronavirus spike proteincomprises a receptor binding domain (RBD) of a spike protein. In someembodiments, the coronavirus is a SARS-CoV-2 coronavirus. In someembodiments, the antibody is administered in combination with a secondpharmaceutical agent.

In certain aspects, the invention provides a method of preventing aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of asynthesized monoclonal antibody, or a functional fragment thereof,comprising a heavy chain having a variable domain and a constant domainand a light chain having a variable and a constant domain, wherein theantibody binds an antigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody neutralizes a coronavirus. In some embodiments, the coronavirusis SARS-CoV-2. In some embodiments, the antibody specifically binds anepitope on the surface of the coronavirus. In some embodiments, theepitope comprises at least a portion of a coronavirus spike protein. Insome embodiments, the at least a portion of a coronavirus spike proteincomprises a receptor binding domain (RBD) of a spike protein. In someembodiments, the coronavirus is a SARS-CoV-2 coronavirus. In someembodiments, the antibody is administered in combination with a secondpharmaceutical agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 7, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 9, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 11, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 33, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 39, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 4, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 8, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 10, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 12, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 26, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 30, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 40, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 4.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 7 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 8.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 9 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 10.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 11 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 12. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 17 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 19 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 21 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 25 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 29 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 30.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 33 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 37 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 38. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 39 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 40. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 43 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 45 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 3 and the light chain variable domain comprises SEQ ID NO: 4. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO: 7and the light chain variable domain comprises SEQ ID NO: 8. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 9 andthe light chain variable domain comprises SEQ ID NO: 10. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 11 andthe light chain variable domain comprises SEQ ID NO: 12. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 17 andthe light chain variable domain comprises SEQ ID NO: 18. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 19 andthe light chain variable domain comprises SEQ ID NO: 20. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 21 andthe light chain variable domain comprises SEQ ID NO: 22. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 25 andthe light chain variable domain comprises SEQ ID NO: 26. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 29 andthe light chain variable domain comprises SEQ ID NO: 30. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 31 andthe light chain variable domain comprises SEQ ID NO: 32. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 33 andthe light chain variable domain comprises SEQ ID NO: 34. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 37 andthe light chain variable domain comprises SEQ ID NO: 38. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 39 andthe light chain variable domain comprises SEQ ID NO: 40. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 43 andthe light chain variable domain comprises SEQ ID NO: 44. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 45 andthe light chain variable domain comprises SEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 3; the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 7; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 9; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 11; or the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 17. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:19; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 21; the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 25; the CDR1, CDR2, and CDR3 regions ofSEQ ID NO: 29; or the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 31. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 33; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 37; the CDR1, CDR2, and CDR3 regions of SEQ ID NO:39; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 43; or the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 45. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 4; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 8; the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 10; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 12; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 18. In some embodiments, the light chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 20; the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 22; the CDR1, CDR2, and CDR3 regions of SEQID NO: 26; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 30; or theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 32. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 34; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 38; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 40; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 44; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 46.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427.

In some embodiments, the antibody specifically binds an epitope on thesurface of the coronavirus. In some embodiments, the epitope comprisesat least a portion of a coronavirus spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises areceptor binding domain (RBD) of a spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises aN-Terminal domain (NTD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a synthesized monoclonal antibody, or a functional fragmentthereof, comprising a heavy chain having a variable domain and aconstant domain and a light chain having a variable domain and aconstant domain, wherein the antibody binds an antigen on a coronavirusparticle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 7, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 9, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 11, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 33, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 39, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 4, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 8, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 10, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 12, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 26, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 30, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 40, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 4.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 7 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 8.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 9 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 10.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 11 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 12. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 17 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 19 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 21 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 25 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 29 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 30. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 31 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 33 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 37 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 38.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 39 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 40. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 43 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 45 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 3 and the light chain variable domain comprises SEQ ID NO: 4. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO: 7and the light chain variable domain comprises SEQ ID NO: 8. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 9 andthe light chain variable domain comprises SEQ ID NO: 10. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 11 andthe light chain variable domain comprises SEQ ID NO: 12. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 17 andthe light chain variable domain comprises SEQ ID NO: 18. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 19 andthe light chain variable domain comprises SEQ ID NO: 20. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 21 andthe light chain variable domain comprises SEQ ID NO: 22. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 25 andthe light chain variable domain comprises SEQ ID NO: 26. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 29 andthe light chain variable domain comprises SEQ ID NO: 30. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 31 andthe light chain variable domain comprises SEQ ID NO: 32. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 33 andthe light chain variable domain comprises SEQ ID NO: 34. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 37 andthe light chain variable domain comprises SEQ ID NO: 38. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 39 andthe light chain variable domain comprises SEQ ID NO: 40. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 43 andthe light chain variable domain comprises SEQ ID NO: 44. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 45 andthe light chain variable domain comprises SEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 3; the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 7; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 9; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 11; or the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 17. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:19; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 21; the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 25; the CDR1, CDR2, and CDR3 regions ofSEQ ID NO: 29; or the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 31. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 33; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 37; the CDR1, CDR2, and CDR3 regions of SEQ ID NO:39; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 43; or the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 45. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 4; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 8; the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 10; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 12; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 18. In some embodiments, the light chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 20; the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 22; the CDR1, CDR2, and CDR3 regions of SEQID NO: 26; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 30; or theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 32. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 34; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 38; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 40; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 44; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 46.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427.

In some embodiments, the antibody specifically binds an epitope on thesurface of the coronavirus. In some embodiments, the epitope comprisesat least a portion of a coronavirus spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises areceptor binding domain (RBD) of a spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises aN-Terminal domain (NTD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus. In some embodiments, thecomposition is administered in combination with a second therapeuticagent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 51, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 55, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 67, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 71, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 75, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 79, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 83, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 87, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 91, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 95, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 99, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 103, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 107, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 115, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 119, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 123, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 127,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 131, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 139, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 143, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 147,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 151, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 155, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 159, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 163,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 167, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 171, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 175, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 179,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:183.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 52,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 56, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 68; a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 72, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 76, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 80, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 84, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 88, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 92, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 96, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 100, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 104, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 108,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 116, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 120, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 124, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 128,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 132, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 140, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 144, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 148,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 152, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 156, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 160, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 164,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 168, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 172, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 176, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 180,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:184.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 53,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 57, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 69, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 73, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 77, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 81, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 85, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 89, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 93, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 97, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 101, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 105, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 109,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 117, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 121, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 125, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 129,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 133, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 141, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 145, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 149,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 153, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 157, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 161, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 165,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 169, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 173, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 177, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 181,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 185.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 54,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 58, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 70, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 74, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 78, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 82, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 86, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 90, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 94, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 98, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 102, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 106, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 110,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 118, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 122, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 126, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 130,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 134, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 142, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 146, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 150,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 154, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 158, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 162, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 166,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 170, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 174, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 178, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 182,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 186.

In some embodiments, variable domain of the first heavy chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 35, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 25, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 19, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 41.

In some embodiments, variable domain of the first light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 28, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 36, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 26, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 20, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 6, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 42.

In some embodiments, variable domain of the second heavy chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 27, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 5, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 19, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 21, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 29, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 35, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 23, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 25, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 37, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 39, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 43, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 9.

In some embodiments, variable domain of the second light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 6, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 30, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 26, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 40, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 10.

In some embodiments, the variable domain of the first heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 51; the CDR1, CDR2, andCDR3 of SEQ ID NO: the CDR1, CDR2, and CDR3 of SEQ ID NO: 67; the CDR1,CDR2, and CDR3 of SEQ ID NO: 71; the CDR1, CDR2, and CDR3 of SEQ ID NO:75; the CDR1, CDR2, and CDR3 of SEQ ID NO: 79; the CDR1, CDR2, and CDR3of SEQ ID NO: 83; the CDR1, CDR2, and CDR3 of SEQ ID NO: 87; the CDR1,CDR2, and CDR3 of SEQ ID NO: 91; the CDR1, CDR2, and CDR3 of SEQ ID NO:95; the CDR1, CDR2, and CDR3 of SEQ ID NO: 99; the CDR1, CDR2, and CDR3of SEQ ID NO: 103; the CDR1, CDR2, and CDR3 of SEQ ID NO: 107; the CDR1,CDR2, and CDR3 of SEQ ID NO: 115; the CDR1, CDR2, and CDR3 of SEQ ID NO:119, the CDR1, CDR2, and CDR3 of SEQ ID NO: 123, the CDR1, CDR2, andCDR3 of SEQ ID NO: 127; the CDR1, CDR2, and CDR3 of SEQ ID NO: 131; theCDR1, CDR2, and CDR3 of SEQ ID NO: 139; the CDR1, CDR2, and CDR3 of SEQID NO: 143; the CDR1, CDR2, and CDR3 of SEQ ID NO: 147; the CDR1, CDR2,and CDR3 of SEQ ID NO: 151; the CDR1, CDR2, and CDR3 of SEQ ID NO: 155;the CDR1, CDR2, and CDR3 of SEQ ID NO: 159; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 163; the CDR1, CDR2, and CDR3 of SEQ ID NO: 167, the CDR1,CDR2, and CDR3 of SEQ ID NO: 171, the CDR1, CDR2, and CDR3 of SEQ ID NO:175, the CDR1, CDR2, and CDR3 of SEQ ID NO: 179, or the CDR1, CDR2, andCDR3 of SEQ ID NO: 183.

In some embodiments, the variable domain of the first light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 52; the CDR1, CDR2, andCDR3 of SEQ ID NO: 56; the CDR1, CDR2, and CDR3 of SEQ ID NO: 68; theCDR1, CDR2, and CDR3 of SEQ ID NO: 72; the CDR1, CDR2, and CDR3 of SEQID NO: 76; the CDR1, CDR2, and CDR3 of SEQ ID NO: 80; the CDR1, CDR2,and CDR3 of SEQ ID NO: 84; the CDR1, CDR2, and CDR3 of SEQ ID NO: 88;the CDR1, CDR2, and CDR3 of SEQ ID NO: 92; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 96; the CDR1, CDR2, and CDR3 of SEQ ID NO: 100; the CDR1,CDR2, and CDR3 of SEQ ID NO: 104; the CDR1, CDR2, and CDR3 of SEQ ID NO:108; the CDR1, CDR2, and CDR3 of SEQ ID NO: 116; the CDR1, CDR2, andCDR3 of SEQ ID NO: 120; the CDR1, CDR2, and CDR3 of SEQ ID NO: 124; theCDR1, CDR2, and CDR3 of SEQ ID NO: 128; the CDR1, CDR2, and CDR3 of SEQID NO: 132; the CDR1, CDR2, and CDR3 of SEQ ID NO: 140; the CDR1, CDR2,and CDR3 of SEQ ID NO: 144; the CDR1, CDR2, and CDR3 of SEQ ID NO: 148;the CDR1, CDR2, and CDR3 of SEQ ID NO: 152; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 156; the CDR1, CDR2, and CDR3 of SEQ ID NO: 160; the CDR1,CDR2, and CDR3 of SEQ ID NO: 164; the CDR1, CDR2, and CDR3 of SEQ ID NO:168, the CDR1, CDR2, and CDR3 of SEQ ID NO: 172, the CDR1, CDR2, andCDR3 of SEQ ID NO: 176, the CDR1, CDR2, and CDR3 of SEQ ID NO: 180, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 184.

In some embodiments, the variable domain of the second heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 53; the CDR1, CDR2, andCDR3 of SEQ ID NO: 57; the CDR1, CDR2, and CDR3 of SEQ ID NO: 69; theCDR1, CDR2, and CDR3 of SEQ ID NO: 73; the CDR1, CDR2, and CDR3 of SEQID NO: 77; the CDR1, CDR2, and CDR3 of SEQ ID NO: 81; the CDR1, CDR2,and CDR3 of SEQ ID NO: 85; the CDR1, CDR2, and CDR3 of SEQ ID NO: 89;the CDR1, CDR2, and CDR3 of SEQ ID NO: 93; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 97; the CDR1, CDR2, and CDR3 of SEQ ID NO: 101; the CDR1,CDR2, and CDR3 of SEQ ID NO: 105; the CDR1, CDR2, and CDR3 of SEQ ID NO:109; the CDR1, CDR2, and CDR3 of SEQ ID NO: 117; the CDR1, CDR2, andCDR3 of SEQ ID NO: 121; the CDR1, CDR2, and CDR3 of SEQ ID NO: 125; theCDR1, CDR2, and CDR3 of SEQ ID NO: 129; the CDR1, CDR2, and CDR3 of SEQID NO: 133; the CDR1, CDR2, and CDR3 of SEQ ID NO: 141; the CDR1, CDR2,and CDR3 of SEQ ID NO: 145; the CDR1, CDR2, and CDR3 of SEQ ID NO: 149;the CDR1, CDR2, and CDR3 of SEQ ID NO: 153; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 157; the CDR1, CDR2, and CDR3 of SEQ ID NO: 161; the CDR1,CDR2, and CDR3 of SEQ ID NO: 165; the CDR1, CDR2, and CDR3 of SEQ ID NO:169, the CDR1, CDR2, and CDR3 of SEQ ID NO: 173, the CDR1, CDR2, andCDR3 of SEQ ID NO: 177, the CDR1, CDR2, and CDR3 of SEQ ID NO: 181, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 185.

In some embodiments, the variable domain of the second light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 54; the CDR1, CDR2, andCDR3 of SEQ ID NO: 58; the CDR1, CDR2, and CDR3 of SEQ ID NO: 70; theCDR1, CDR2, and CDR3 of SEQ ID NO: 74; the CDR1, CDR2, and CDR3 of SEQID NO: 78; the CDR1, CDR2, and CDR3 of SEQ ID NO: 82; the CDR1, CDR2,and CDR3 of SEQ ID NO: 86; the CDR1, CDR2, and CDR3 of SEQ ID NO: 90;the CDR1, CDR2, and CDR3 of SEQ ID NO: 94; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 98; the CDR1, CDR2, and CDR3 of SEQ ID NO: 102; the CDR1,CDR2, and CDR3 of SEQ ID NO: 106; the CDR1, CDR2, and CDR3 of SEQ ID NO:110; the CDR1, CDR2, and CDR3 of SEQ ID NO: 118; the CDR1, CDR2, andCDR3 of SEQ ID NO: 122; the CDR1, CDR2, and CDR3 of SEQ ID NO: 126; theCDR1, CDR2, and CDR3 of SEQ ID NO: 130; the CDR1, CDR2, and CDR3 of SEQID NO: 134; the CDR1, CDR2, and CDR3 of SEQ ID NO: 142; the CDR1, CDR2,and CDR3 of SEQ ID NO: 146; the CDR1, CDR2, and CDR3 of SEQ ID NO: 150;the CDR1, CDR2, and CDR3 of SEQ ID NO: 154; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 158; the CDR1, CDR2, and CDR3 of SEQ ID NO: 162, the CDR1,CDR2, and CDR3 of SEQ ID NO: 166; the CDR1, CDR2, and CDR3 of SEQ ID NO:170, the CDR1, CDR2, and CDR3 of SEQ ID NO: 174, the CDR1, CDR2, andCDR3 of SEQ ID NO: 178, the CDR1, CDR2, and CDR3 of SEQ ID NO: 182, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 186.

In some embodiments, the molecule comprises SEQ ID NO: 51, SEQ ID NO:52, SEQ ID NO: 53, and SEQ ID NO: 54. In some embodiments, the moleculecomprises SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO:58. In some embodiments, the molecule comprises SEQ ID NO: 67, SEQ IDNO: 68, SEQ ID NO: 69, and SEQ ID NO: 70. In some embodiments, themolecule comprises SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, and SEQID NO: 74. In some embodiments, the molecule comprises SEQ ID NO: 75,SEQ ID NO: 76, SEQ ID NO: 77, and SEQ ID NO: 78. In some embodiments,the molecule comprises SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, andSEQ ID NO: 82. In some embodiments, the molecule comprises SEQ ID NO:83, SEQ ID NO: 84, SEQ ID NO: 85, and SEQ ID NO: 86. In someembodiments, the molecule comprises SEQ ID NO: 87, SEQ ID NO: 88, SEQ IDNO: 89, and SEQ ID NO: 90. In some embodiments, the molecule comprisesSEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94. In someembodiments, the molecule comprises SEQ ID NO: 95, SEQ ID NO: 96, SEQ IDNO: 97, and SEQ ID NO: 98. In some embodiments, the molecule comprisesSEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. Insome embodiments, the molecule comprises SEQ ID NO: 103, SEQ ID NO: 104,SEQ ID NO: 105, and SEQ ID NO: 106. In some embodiments, the moleculecomprises SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, and SEQ ID NO:110. In some embodiments, the molecule comprises SEQ ID NO: 115, SEQ IDNO: 116, SEQ ID NO: 117, and SEQ ID NO: 118. In some embodiments, themolecule comprises SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, andSEQ ID NO: 122.

In some embodiments, the molecule comprises SEQ ID NO: 123, SEQ ID NO:124, SEQ ID NO: 125, and SEQ ID NO: 126. In some embodiments, themolecule comprises SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, andSEQ ID NO: 130. In some embodiments, the molecule comprises SEQ ID NO:131, SEQ ID NO: 132, SEQ ID NO: 133, and SEQ ID NO: 133. In someembodiments, the molecule comprises SEQ ID NO: 139, SEQ ID NO: 140, SEQID NO: 141, and SEQ ID NO: 142. In some embodiments, the moleculecomprises SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO:146. In some embodiments, the molecule comprises SEQ ID NO: 147, SEQ IDNO: 148, SEQ ID NO: 149, and SEQ ID NO: 150. In some embodiments, themolecule comprises SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, andSEQ ID NO: 154. In some embodiments, the molecule comprises SEQ ID NO:155, SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158. In someembodiments, the molecule comprises SEQ ID NO: 159, SEQ ID NO: 160, SEQID NO: 161, and SEQ ID NO: 162. In some embodiments, the moleculecomprises SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO:166. In some embodiments, the molecule comprises SEQ ID NO: 167, SEQ IDNO: 168, SEQ ID NO: 169, and SEQ ID NO: 170. In some embodiments, themolecule comprises SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, andSEQ ID NO: 174. In some embodiments, the molecule comprises SEQ ID NO:175, SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178. In someembodiments, the molecule comprises SEQ ID NO: 179, SEQ ID NO: 180, SEQID NO: 181, and SEQ ID NO: 182. In some embodiments, the moleculecomprises SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO:186.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427.

In some embodiments, the molecule specifically recognizes a firstepitope and a second epitope on a SARS-CoV-2 particle. In someembodiments, the first epitope comprises at least a portion of areceptor binding domain (RBD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the second epitope comprises at least aportion of a N-terminal domain (NTD) on a spike protein of a SARS-CoV-2particle.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a composition comprising abispecific molecule comprising a first polypeptide chain and a secondpolypeptide chain, wherein: the first polypeptide chain comprises: afirst light chain comprising a variable domain and a constant domain; afirst heavy chain comprising a variable domain and a constant domain;the second polypeptide chain comprises: a second light chain comprisinga variable domain and a constant domain; and a second heavy chaincomprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 51, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 55, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 67, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 71, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 75, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 79, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 83, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 87, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 91, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 95, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 99, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 103, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 107, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 115, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 119, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 123, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 127,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 131, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 139, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 143, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 147,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 151, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 155, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 159, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 163,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 167, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 171, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 175, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 179,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:183.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 52,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 56, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 68; a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 72, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 76, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 80, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 84, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 88, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 92, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 96, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 100, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 104, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 108,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 116, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 120, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 124, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 128,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 132, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 140, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 144, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 148,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 152, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 156, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 160, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 164,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 168, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 172, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 176, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 180,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:184.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 53,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 57, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 69, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 73, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 77, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 81, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 85, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 89, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 93, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 97, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 101, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 105, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 109,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 117, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 121, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 125, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 129,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 133, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 141, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 145, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 149,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 153, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 157, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 161, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 165,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 169, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 173, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 177, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 181,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 185.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 54,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 58, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 70, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 74, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 78, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 82, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 86, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 90, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 94, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 98, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 102, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 106, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 110,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 118, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 122, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 126, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 130,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 134, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 142, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 146, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 150,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 154, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 158, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 162, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 166,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 170, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 174, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 178, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 182,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 186.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 35, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 25, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 17, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 37, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 19, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 13, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 5, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 21, or a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 41.

In some embodiments, the variable domain of the first light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 28, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 18, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 6, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 22, or a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 42.

In some embodiments, the variable domain of the second heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 15, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 5, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 15, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 35, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 23, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 37, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 39, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 43, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 9.

In some embodiments, variable domain of the second light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 6, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 30, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 26, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 40, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 10.

In some embodiments, the variable domain of the first heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 51; the CDR1, CDR2, andCDR3 of SEQ ID NO: the CDR1, CDR2, and CDR3 of SEQ ID NO: 67; the CDR1,CDR2, and CDR3 of SEQ ID NO: 71; the CDR1, CDR2, and CDR3 of SEQ ID NO:75; the CDR1, CDR2, and CDR3 of SEQ ID NO: 79; the CDR1, CDR2, and CDR3of SEQ ID NO: 83; the CDR1, CDR2, and CDR3 of SEQ ID NO: 87; the CDR1,CDR2, and CDR3 of SEQ ID NO: 91; the CDR1, CDR2, and CDR3 of SEQ ID NO:95; the CDR1, CDR2, and CDR3 of SEQ ID NO: 99; the CDR1, CDR2, and CDR3of SEQ ID NO: 103; the CDR1, CDR2, and CDR3 of SEQ ID NO: 107; the CDR1,CDR2, and CDR3 of SEQ ID NO: 115; the CDR1, CDR2, and CDR3 of SEQ ID NO:119, the CDR1, CDR2, and CDR3 of SEQ ID NO: 123, the CDR1, CDR2, andCDR3 of SEQ ID NO: 127; the CDR1, CDR2, and CDR3 of SEQ ID NO: 131; theCDR1, CDR2, and CDR3 of SEQ ID NO: 139; the CDR1, CDR2, and CDR3 of SEQID NO: 143; the CDR1, CDR2, and CDR3 of SEQ ID NO: 147; the CDR1, CDR2,and CDR3 of SEQ ID NO: 151; the CDR1, CDR2, and CDR3 of SEQ ID NO: 155;the CDR1, CDR2, and CDR3 of SEQ ID NO: 159; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 163; the CDR1, CDR2, and CDR3 of SEQ ID NO: 167, the CDR1,CDR2, and CDR3 of SEQ ID NO: 171, the CDR1, CDR2, and CDR3 of SEQ ID NO:175, the CDR1, CDR2, and CDR3 of SEQ ID NO: 179, or the CDR1, CDR2, andCDR3 of SEQ ID NO: 183.

In some embodiments, the variable domain of the first light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 52; the CDR1, CDR2, andCDR3 of SEQ ID NO: 56; the CDR1, CDR2, and CDR3 of SEQ ID NO: 68; theCDR1, CDR2, and CDR3 of SEQ ID NO: 72; the CDR1, CDR2, and CDR3 of SEQID NO: 76; the CDR1, CDR2, and CDR3 of SEQ ID NO: 80; the CDR1, CDR2,and CDR3 of SEQ ID NO: 84; the CDR1, CDR2, and CDR3 of SEQ ID NO: 88;the CDR1, CDR2, and CDR3 of SEQ ID NO: 92; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 96; the CDR1, CDR2, and CDR3 of SEQ ID NO: 100; the CDR1,CDR2, and CDR3 of SEQ ID NO: 104; the CDR1, CDR2, and CDR3 of SEQ ID NO:108; the CDR1, CDR2, and CDR3 of SEQ ID NO: 116; the CDR1, CDR2, andCDR3 of SEQ ID NO: 120; the CDR1, CDR2, and CDR3 of SEQ ID NO: 124; theCDR1, CDR2, and CDR3 of SEQ ID NO: 128; the CDR1, CDR2, and CDR3 of SEQID NO: 132; the CDR1, CDR2, and CDR3 of SEQ ID NO: 140; the CDR1, CDR2,and CDR3 of SEQ ID NO: 144; the CDR1, CDR2, and CDR3 of SEQ ID NO: 148;the CDR1, CDR2, and CDR3 of SEQ ID NO: 152; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 156; the CDR1, CDR2, and CDR3 of SEQ ID NO: 160; the CDR1,CDR2, and CDR3 of SEQ ID NO: 164; the CDR1, CDR2, and CDR3 of SEQ ID NO:168, the CDR1, CDR2, and CDR3 of SEQ ID NO: 172, the CDR1, CDR2, andCDR3 of SEQ ID NO: 176, the CDR1, CDR2, and CDR3 of SEQ ID NO: 180, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 184.

In some embodiments, the variable domain of the second heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 53; the CDR1, CDR2, andCDR3 of SEQ ID NO: 57; the CDR1, CDR2, and CDR3 of SEQ ID NO: 69; theCDR1, CDR2, and CDR3 of SEQ ID NO: 73; the CDR1, CDR2, and CDR3 of SEQID NO: 77; the CDR1, CDR2, and CDR3 of SEQ ID NO: 81; the CDR1, CDR2,and CDR3 of SEQ ID NO: 85; the CDR1, CDR2, and CDR3 of SEQ ID NO: 89;the CDR1, CDR2, and CDR3 of SEQ ID NO: 93; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 97; the CDR1, CDR2, and CDR3 of SEQ ID NO: 101; the CDR1,CDR2, and CDR3 of SEQ ID NO: 105; the CDR1, CDR2, and CDR3 of SEQ ID NO:109; the CDR1, CDR2, and CDR3 of SEQ ID NO: 117; the CDR1, CDR2, andCDR3 of SEQ ID NO: 121; the CDR1, CDR2, and CDR3 of SEQ ID NO: 125; theCDR1, CDR2, and CDR3 of SEQ ID NO: 129; the CDR1, CDR2, and CDR3 of SEQID NO: 133; the CDR1, CDR2, and CDR3 of SEQ ID NO: 141; the CDR1, CDR2,and CDR3 of SEQ ID NO: 145; the CDR1, CDR2, and CDR3 of SEQ ID NO: 149;the CDR1, CDR2, and CDR3 of SEQ ID NO: 153; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 157; the CDR1, CDR2, and CDR3 of SEQ ID NO: 161; the CDR1,CDR2, and CDR3 of SEQ ID NO: 165; the CDR1, CDR2, and CDR3 of SEQ ID NO:169, the CDR1, CDR2, and CDR3 of SEQ ID NO: 173, the CDR1, CDR2, andCDR3 of SEQ ID NO: 177, the CDR1, CDR2, and CDR3 of SEQ ID NO: 181, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 185.

In some embodiments, the variable domain of the second light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 54; the CDR1, CDR2, andCDR3 of SEQ ID NO: 58; the CDR1, CDR2, and CDR3 of SEQ ID NO: 70; theCDR1, CDR2, and CDR3 of SEQ ID NO: 74; the CDR1, CDR2, and CDR3 of SEQID NO: 78; the CDR1, CDR2, and CDR3 of SEQ ID NO: 82; the CDR1, CDR2,and CDR3 of SEQ ID NO: 86; the CDR1, CDR2, and CDR3 of SEQ ID NO: 90;the CDR1, CDR2, and CDR3 of SEQ ID NO: 94; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 98; the CDR1, CDR2, and CDR3 of SEQ ID NO: 102; the CDR1,CDR2, and CDR3 of SEQ ID NO: 106; the CDR1, CDR2, and CDR3 of SEQ ID NO:110; the CDR1, CDR2, and CDR3 of SEQ ID NO: 118; the CDR1, CDR2, andCDR3 of SEQ ID NO: 122; the CDR1, CDR2, and CDR3 of SEQ ID NO: 126; theCDR1, CDR2, and CDR3 of SEQ ID NO: 130; the CDR1, CDR2, and CDR3 of SEQID NO: 134; the CDR1, CDR2, and CDR3 of SEQ ID NO: 142; the CDR1, CDR2,and CDR3 of SEQ ID NO: 146; the CDR1, CDR2, and CDR3 of SEQ ID NO: 150;the CDR1, CDR2, and CDR3 of SEQ ID NO: 154; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 158; the CDR1, CDR2, and CDR3 of SEQ ID NO: 162, the CDR1,CDR2, and CDR3 of SEQ ID NO: 166; the CDR1, CDR2, and CDR3 of SEQ ID NO:170, the CDR1, CDR2, and CDR3 of SEQ ID NO: 174, the CDR1, CDR2, andCDR3 of SEQ ID NO: 178, the CDR1, CDR2, and CDR3 of SEQ ID NO: 182, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 186.

In some embodiments, the molecule comprises SEQ ID NO: 51, SEQ ID NO:52, SEQ ID NO: 53, and SEQ ID NO: 54. In some embodiments, the moleculecomprises SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO:58. In some embodiments, the molecule comprises SEQ ID NO: 67, SEQ IDNO: 68, SEQ ID NO: 69, and SEQ ID NO: In some embodiments, the moleculecomprises SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO:74. In some embodiments, the molecule comprises SEQ ID NO: SEQ ID NO:76, SEQ ID NO: 77, and SEQ ID NO: 78. In some embodiments, the moleculecomprises SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO:82. In some embodiments, the molecule comprises SEQ ID NO: 83, SEQ IDNO: 84, SEQ ID NO: 85, and SEQ ID NO: 86. In some embodiments, themolecule comprises SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, and SEQID NO: 90. In some embodiments, the molecule comprises SEQ ID NO: 91,SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94. In some embodiments,the molecule comprises SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, andSEQ ID NO: 98. In some embodiments, the molecule comprises SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. In someembodiments, the molecule comprises SEQ ID NO: 103, SEQ ID NO: 104, SEQID NO: 105, and SEQ ID NO: 106. In some embodiments, the moleculecomprises SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, and SEQ ID NO:110. In some embodiments, the molecule comprises SEQ ID NO: 115, SEQ IDNO: 116, SEQ ID NO: 117, and SEQ ID NO: 118.

In some embodiments, the molecule comprises SEQ ID NO: 119, SEQ ID NO:120, SEQ ID NO: 121, and SEQ ID NO: 122. In some embodiments, themolecule comprises SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, andSEQ ID NO: 126. In some embodiments, the molecule comprises SEQ ID NO:127, SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130. In someembodiments, the molecule comprises SEQ ID NO: 131, SEQ ID NO: 132, SEQID NO: 133, and SEQ ID NO: 133. In some embodiments, the moleculecomprises SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, and SEQ ID NO:142. In some embodiments, the molecule comprises SEQ ID NO: 143, SEQ IDNO: 144, SEQ ID NO: 145, and SEQ ID NO: 146. In some embodiments, themolecule comprises SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, andSEQ ID NO: 150. In some embodiments, the molecule comprises SEQ ID NO:151, SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154. In someembodiments, the molecule comprises SEQ ID NO: 155, SEQ ID NO: 156, SEQID NO: 157, and SEQ ID NO: 158. In some embodiments, the moleculecomprises SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO:162. In some embodiments, the molecule comprises SEQ ID NO: 163, SEQ IDNO: 164, SEQ ID NO: 165, and SEQ ID NO: 166. In some embodiments, themolecule comprises SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, andSEQ ID NO: 170. In some embodiments, the molecule comprises SEQ ID NO:171, SEQ ID NO: 172, SEQ ID NO: 173, and SEQ ID NO: 174. In someembodiments, the molecule comprises SEQ ID NO: 175, SEQ ID NO: 176, SEQID NO: 177, and SEQ ID NO: 178. In some embodiments, the moleculecomprises SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO:182. In some embodiments, the molecule comprises SEQ ID NO: 183, SEQ IDNO: 184, SEQ ID NO: 185, and SEQ ID NO: 186.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 41. In some embodiments, the heavy chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 35. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23. In some embodiments,the heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 27. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 6. In some embodiments, the light chain variabledomain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 42. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 36. In some embodiments, the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 2.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 14. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 28. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 5 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 6. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 41 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 42. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 35 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 36.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 1 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 2.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 23 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 5 and the light chain variable domain comprises SEQ ID NO: 6. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO:41 and the light chain variable domain comprises SEQ ID NO: 42. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 35 andthe light chain variable domain comprises SEQ ID NO: 36. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 1 andthe light chain variable domain comprises SEQ ID NO: 2. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 23 andthe light chain variable domain comprises SEQ ID NO: 24. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 13 andthe light chain variable domain comprises SEQ ID NO: 14. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 27 andthe light chain variable domain comprises SEQ ID NO: 28. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 5. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:41. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 23. In some embodiments, the heavychain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 13. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 27.

In some embodiments, the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 6. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 42. In some embodiments, the light chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 36. In someembodiments, the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 2. In some embodiments, the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:24. In some embodiments, the light chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 14. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 28. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 5 and the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 6. In some embodiments, the heavy chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 41 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:42. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 35 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:36. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 23 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 24. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 13 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 14. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 27 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 28.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a N-Terminaldomain (NTD) of a spike protein. In some embodiments, the coronavirus isa SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a synthesized monoclonal antibody, or a functional fragmentthereof, comprising a heavy chain having a variable domain and aconstant domain and a light chain having a variable domain and aconstant domain, wherein the antibody binds an antigen on a coronavirusparticle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 41. In some embodiments, the heavy chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 35. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23. In some embodiments,the heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13. In someembodiments, the heavy chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27.In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 6.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 42. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 36. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 2. In some embodiments, the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 24. In some embodiments, thelight chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14. In some embodiments,the light chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 6.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 41 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 42. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 36. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 1 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 2. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 23 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 13 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 5 and the light chain variable domain comprises SEQ ID NO: 6. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO:41 and the light chain variable domain comprises SEQ ID NO: 42. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 35 andthe light chain variable domain comprises SEQ ID NO: 36. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 1 andthe light chain variable domain comprises SEQ ID NO: 2. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 23 andthe light chain variable domain comprises SEQ ID NO: 24. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 13 andthe light chain variable domain comprises SEQ ID NO: 14.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 27 and the light chain variable domain comprises SEQ ID NO: 28. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: In some embodiments, the heavychain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 41. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 1. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 23. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:13. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 27. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 6. In some embodiments, the light chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 42. In someembodiments, the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 36. In some embodiments, the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2. In some embodiments, the light chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 24.

In some embodiments, the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 14. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 28. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 5 and the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 6. In some embodiments, the heavy chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 41 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:42. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 35 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:36. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 23 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:24. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 13 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:14. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 27 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:28.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a N-Terminaldomain (NTD) of a spike protein. In some embodiments, the coronavirus isa SARS-CoV-2 coronavirus. In some embodiments, the antibody isadministered in combination with a second pharmaceutical agent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain. In some embodiments, the firstpolypeptide chain and the second polypeptide chain are covalently bondedto one another.

In some embodiments, the first heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 47,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 111, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 135, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 187, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 211.In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 48,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 112, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 136, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 188, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 212.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 49,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 113, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 137, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 189, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 213.In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 50,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 114, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 138, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 190, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 214.In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 13.

In some embodiments, the variable domain of the first light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 36, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14. In some embodiments, thevariable domain of the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 43. In some embodiments, the variable domainof the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 46,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 47; CDR1, CDR2, and CDR3 ofSEQ ID NO: 111; CDR1, CDR2, and CDR3 of SEQ ID NO: 135; CDR1, CDR2, andCDR3 of SEQ ID NO: 187; or CDR1, CDR2, and CDR3 of SEQ ID NO: 211. Insome embodiments, the variable domain of the first light chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 48, CDR1, CDR2, and CDR3 of SEQ IDNO: 112; CDR1, CDR2, and CDR3 of SEQ ID NO: 136; CDR1, CDR2, and CDR3 ofSEQ ID NO: 188; or CDR1, CDR2, and CDR3 of SEQ ID NO: 212. In someembodiments, the variable domain of the second heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 49, CDR1, CDR2, and CDR3 of SEQ IDNO: 113; CDR1, CDR2, and CDR3 of SEQ ID NO: 137; CDR1, CDR2, and CDR3 ofSEQ ID NO: 189; or CDR1, CDR2, and CDR3 of SEQ ID NO: 213. In someembodiments, the variable domain of the second light chain comprisesCDR1, CDR2, and CDR3 SEQ ID NO: 50, CDR1, CDR2, and CDR3 of SEQ ID NO:114; CDR1, CDR2, and CDR3 of SEQ ID NO: 138; CDR1, CDR2, and CDR3 of SEQID NO: 190; or CDR1, CDR2, and CDR3 of SEQ ID NO: 214.

In some embodiments, the molecule comprises SEQ ID NO: 47, SEQ ID NO:48, SEQ ID NO: 49, and SEQ ID NO: 50. In some embodiments, the moleculecomprises SEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO:114. In some embodiments, the molecule comprises SEQ ID NO: 135, SEQ IDNO: 135, SEQ ID NO: 137, and SEQ ID NO: 138. In some embodiments, themolecule comprises SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, andSEQ ID NO: 190. In some embodiments, the molecule comprises SEQ ID NO:211, SEQ ID NO: 212, SEQ ID NO: 213, and SEQ ID NO: 214.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a composition comprising abispecific molecule comprising a first polypeptide chain and a secondpolypeptide chain, wherein: the first polypeptide chain comprises: afirst light chain comprising a variable domain and a constant domain; afirst heavy chain comprising a variable domain and a constant domain;the second polypeptide chain comprises: a second light chain comprisinga variable domain and a constant domain; and a second heavy chaincomprising a variable domain and a constant domain. In some embodiments,the first polypeptide chain and the second polypeptide chain arecovalently bonded to one another.

In some embodiments, the first heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 47,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 111, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 135, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 187, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 211.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 48,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 112, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 136, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 188, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 212.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 49,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 113, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 137, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 189, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 213.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 50,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 114, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 138, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 190, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 214.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 13. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the variable domain of the secondheavy chain comprises a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 13, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 45, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43.

In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 14, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 46, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 47; CDR1, CDR2, and CDR3 ofSEQ ID NO: 111; CDR1, CDR2, and CDR3 of SEQ ID NO: 135; CDR1, CDR2, andCDR3 of SEQ ID NO: 187; or CDR1, CDR2, and CDR3 of SEQ ID NO: 211. Insome embodiments, the variable domain of the first light chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 48, CDR1, CDR2, and CDR3 of SEQ IDNO: 112; CDR1, CDR2, and CDR3 of SEQ ID NO: 136; CDR1, CDR2, and CDR3 ofSEQ ID NO: 188; or CDR1, CDR2, and CDR3 of SEQ ID NO: 212. In someembodiments, the variable domain of the second heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 49, CDR1, CDR2, and CDR3 of SEQ IDNO: 113; CDR1, CDR2, and CDR3 of SEQ ID NO: 137; CDR1, CDR2, and CDR3 ofSEQ ID NO: 189; or CDR1, CDR2, and CDR3 of SEQ ID NO: 213. In someembodiments, the variable domain of the second light chain comprisesCDR1, CDR2, and CDR3 SEQ ID NO: 50, CDR1, CDR2, and CDR3 of SEQ ID NO:114; CDR1, CDR2, and CDR3 of SEQ ID NO: 138; CDR1, CDR2, and CDR3 of SEQID NO: 190; or CDR1, CDR2, and CDR3 of SEQ ID NO: 214. In someembodiments, the molecule comprises SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, and SEQ ID NO: 50. In some embodiments, the molecule comprisesSEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO: 114. Insome embodiments, the molecule comprises SEQ ID NO: 135, SEQ ID NO: 135,SEQ ID NO: 137, and SEQ ID NO: 138. In some embodiments, the moleculecomprises SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, and SEQ ID NO:190. In some embodiments, the molecule comprises SEQ ID NO: 211, SEQ IDNO: 212, SEQ ID NO: 213, and SEQ ID NO: 214.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427.

In some embodiments, the molecule specifically recognizes a firstepitope and a second epitope on a SARS-CoV-2 particle. In someembodiments, the first epitope comprises at least a portion of areceptor binding domain (RBD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the second epitope comprises at least aportion of a N-terminal domain (NTD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the composition is administered incombination with a second therapeutic agent.

BRIEF DESCRIPTION OF FIGURES

The patent or application file contains at least one drawing originallyin color. To conform to the requirements for PCT patent applications,many of the figures presented herein are black and white representationsof images originally created in color.

FIGS. 1A-C show images of coronavirus. FIG. 1A shows a SARS-CoV-2 viralparticle schematic diagram. FIG. 1B shows a spike protein trimerstructure. FIG. 1C shows an electronic micrograph of coronavirusparticles. The arrow denotes the viral spike protein on the viralmembrane.

FIGS. 2A-G show individual antibody responses to SARS-CoV-2 virus. FIGS.2A-F shows ELISA binding assays in which various COVID-19 patient plasmasamples (indicated by different colored lines) were tested for theirability to bind to SARS-CoV-2 nucleocapsid antigen (FIGS. 2A and D),SARS-CoV-2 envelope trimer antigen (FIGS. 2B and E), and SARS-CoVenvelope trimer antigen (FIGS. 2C and F). FIGS. 2A-C show responses forpatients with severe disease. FIGS. 2D-F show responses for patientswith non-severe disease. FIG. 2G shows that a higher SARS-CoV-2 antibodyresponses are present in plasma samples of patients with severe COVID-19as compared to patients with non-severe COVID-19.

FIGS. 3A-J show antibody responses that neutralize SARS-CoV-2 potently.FIGS. 3A-F show individual neutralization assays for patients withsevere disease (FIGS. 3A-C) and patients with non-severe disease (FIGS.3D-F). FIGS. 3A and D show neutralization of SARS-CoV-2 pseudovirus.FIGS. 3B and E show neutralization of SARS-CoV pseudovirus. FIGS. 3C andF show neutralization of SARS-CoV-2 live virus. FIG. 3G shows a plot ofthe infective dose (ID₅₀), or the estimated number of virus particlesrequired to produce a 50% infection, obtained from FIGS. 3A-F. FIGS.3H-J show correlation of the IC₅₀ values obtained by pseudovirusneutralization assays with live virus neutralization IC₅₀ (FIG. 311 ),half-maximal plasma dilution (FIG. 3I), and 1:400 OD₄₅₀ (FIG. 3J).

FIGS. 4A-C show schematics for identifying potent neutralizingantibodies against COVID-19. FIG. 4A shows a schematic of producingpotent neutralizing antibodies. FIG. 4B shows memory B cells sorted froma healthy individual and a COVID-19 patient. FIG. 4C shows a table ofseven patient donors and the number of antibodies isolated from eachdonor.

FIGS. 5A-D show binding and neutralization assays of mAbs against theSARS-CoV-2 virus. FIG. 5A shows a binding assay of synthesizedantibodies with the SARS-CoV-2 spike protein trimer. FIG. 5B shows abinding assay of synthesized antibodies with the SARS-CoV-2 receptorbinding domain. FIG. 5C shows neutralization assay of synthesizedantibodies with SARS-CoV-2 pseudovirus. FIG. 5D shows neutralizationassay of synthesized antibodies with SARS-CoV-2 live virus.

FIGS. 6A-F show epitope mapping of SARS-CoV-2 specific monoclonalantibodies by competition ELISA assay. FIGS. 6A-C show individualsynthesized mAbs binding affinity to the receptor-binding domain (RBD),with antibody numbers 2-4, 2-15, and 2-38 specifically binding to theRBD. FIGS. 6D-F show individual synthesized mAbs binding affinity to thereceptor-binding domain (RBD), with antibody numbers 2-51, 4-8, and 4-32showing no binding affinity to the RBD.

FIGS. 7A-E show surface plasmon resonance (SPR) assay for mAb binding tothe spike protein trimers. Each panel represents the binding affinityand binding kinetics of the indicated monoclonal antibody (i.e., 2-4,2-15, 2-38, etc.) to the SARS-CoV-2 envelope timer. Colored linesindicated different dilutions of the respective antibody tested. FIG. 7Ashows mAb 2-4. FIG. 7B shows mAb 2-15. FIG. 7C shows mAb 2-38. FIG. 7Dshows mAb 2-51. FIG. 7E shows mAb 4-8.

FIGS. 8A-D show initial screenings of mAbs that bind and neutralize theSARS-CoV-2 virus. FIG. 8A shows mAbs binding to spike trimer protein.FIG. 8B shows mAbs binding to the receptor-binding domain (RBD). FIG. 8Cshows IC₅₀ values for pseudotyped virus infection. FIG. 8D shows percentinhibition values for live virus infection.

FIG. 9 shows a summary of the SARS-CoV-2-specific mAb screening. Numberof most potent neutralizing mAbs: 17.

FIGS. 10A-I show binding of potent neutralizing mAbs to spike proteintrimer, RBD and N-terminal domain (NTD). FIGS. 10A, D, and G showbinding to spike protein trimer. FIGS. 10B, E, and H show binding to theRBD. FIGS. 10C, F, and I show binding to the NTD. FIGS. 10A-C showbinding of mAbs, which potently bind the RBD. FIGS. 10D-F show bindingof mAbs, which potently bind the NTD. FIGS. 10G-I show binding of mAb,which bind epitopes other than the RBD or the NTD.

FIGS. 11A-F show SARS-CoV-2 neutralization activity of select mAbs. FIG.11A shows neutralization activity of RBD-targeting mAbs neutralizing apseudovirus infection. FIG. 11B shows neutralization activity ofNTD-targeting mAbs neutralizing a pseudovirus infection. FIG. 11C showsneutralization activity of mAbs, which target epitopes other than theRBD or the NTD, neutralizing a pseudovirus infection. FIG. 11D showsneutralization activity of RBD-targeting mAbs neutralizing a live virusinfection. FIG. 11E shows neutralization activity of NTD-targeting mAbsneutralizing a live virus infection.

FIG. 11F shows neutralization activity of mAbs, which target epitopesother than the RBD or the NTD, neutralizing a live virus infection.

FIGS. 12A-B show a CryoEM structure of an RBD-targeting monoclonalantibody. FIG. 12A shows a side view of the mAb. FIG. 12B shows a topview of the mAb.

FIGS. 13A-B show a CryoEM structure of an NTD-targeting monoclonalantibody. FIG. 13A shows a side view of the mAb. FIG. 13B shows a topview of the mAb.

FIG. 14 shows three SARS-CoV-2 neutralizing epitope clusters identifiedon the spike protein trimer.

FIGS. 15A-E show isolation of SARS-CoV-2 mAbs from infected patientswith severe disease. FIG. 15A shows plasma neutralization profile of 40patients against SARS-CoV-2 pseudovirus (highlighted are 5 topneutralizers chosen). All 252 transfection supernatants were screenedfor binding to S trimer and RBD, as well as for neutralization againstSARS-CoV-2 pseudovirus and live virus. For pseudovirus neutralization,the 50% inhibitory dilutions (IC₅₀) of each supernatant were plotted.For live virus, semi-quantitative representation of the inhibition at adilution of 1:50, with neutralization levels ranging from (−) for noneto (+++) for complete neutralization, was plotted. Potent antibodieslater identified are marked by vertical lines and labelled at thebottom. The antibodies from each patient are formatted or colored as inFIG. 15A. FIG. 15B shows s trimer binding. FIG. 15C shows RBD binding.FIG. 15D shows pseudovirus neutralization. FIG. 15E shows live virusneutralization.

FIGS. 16A-O show characterization of SARS-CoV-2 potent neutralizingmAbs. FIGS. 16A, D, and G show binding profiles of 19 purified potentneutralizing mAbs against SARS-CoV-2 S trimer (left). FIGS. 16B, E, andH show binding profiles of 19 purified potent neutralizing mAbs againstSARS-CoV-2 RBD (middle). FIGS. 16C, F, and I show binding profiles of 19purified potent neutralizing mAbs against SARS-CoV-2 NTD (right). Notethat mAb 2-30 bound multiple proteins at high concentrations. FIG. 16Jshows pseudovirus neutralization against SARS-CoV-2 RBD. FIG. 16K showspseudovirus neutralization against SARS-CoV-2 NTD. FIG. 16L showspseudovirus neutralization against other epitopes on the SARS-CoV-2virion. FIG. 16M shows live virus neutralization against SARS-CoV-2 RBD.FIG. 16N shows live virus neutralization against SARS-CoV-2 NTD. FIG.16O shows live virus neutralization against other epitopes on theSARS-CoV-2 virion. The neutralization profiles are for the 19 purifiedmAbs. Single replicate of the binding experiment and triplicates ofneutralization are presented as mean±SEM.

FIGS. 17A-D show epitope mapping of select neutralizing andnon-neutralizing mAbs. Competition results of non-RBD binders (FIG. 17A)and RBD binders (FIG. 17B) in blocking ACE2 or biotinylated mAb bindingto the S trimer. In addition, the ability to bind NTD and RBD of eachmAb is shown. The numbers in each box show the area under eachcompetition curve (AUC) as tested by ELISA. +/− indicates binding/nobinding of the mAb to the protein. FIG. 17C shows a Venn diagraminterpretation of results from FIG. 17B. FIG. 17D shows a Venn diagraminterpretation of results from FIG. 17B.

FIGS. 18A-D show Cryo-EM reconstructions of Fab-spike complexes andvisualization of neutralizing epitopes on the spike surface. FIG. 18Ashows a Cryo-EM 3D reconstruction of antibody 2-4 in complex with Strimer at 3.2 Å overall resolution. Density is colored according tospike domain with RBD in green, NTD in orange, with other regionscolored grey. FIG. 18B shows a Cryo-EM reconstruction of antibody 4-8 incomplex with S trimer (ribbon diagram, colored as in a) at 3.9 Å overallresolution, with RBDs in the “all-down” configuration. The resolution ofantibody density is limited by molecular motion. Although the binding ofFab to NTD and antibody position are clear, the identities of heavy andlight chain are uncertain. FIG. 18C shows a Cryo-EM reconstruction ofthe antibody 2-43 in complex with S trimer at 7.8 Å resolution reveals aquaternary epitope involving RBD from one subunit and NTD from the next.FIG. 18D shows mapping of the Venn diagrams from FIG. 17B onto thesurface of the viral spike.

FIG. 19 shows Patient information. Abbreviation: ARDS, acute respiratorydistress syndrome; MV, mechanical ventilation; hsCRP, high sensitivityC-reactive protein, ULN>10 mg/L; ESR, erythrocyte sedimentation rate,ULN=20 mm/hr; Interleukin 6, ULN=5 pg/mL; Ferritin, ULN=150 ng/mL;D-dimer quantitative ULN=0.8 μg/mL FEU.

FIG. 20 shows summary of mAb screening.

FIG. 21 shows Cryo-EM data collection, refinement, and validationstatistics.

FIGS. 22A-C show SARS-CoV-2 S trimer-specific antibody isolationstrategy. FIG. 22A shows a schema for isolating of S trimer-specificmAbs from memory B cells in the blood of infected patients. FIG. 22Bshows sorting results on the isolation of S trimer-specific memory Bcells using flow cytometry. FIG. 22C shows magnified representation ofthe panel of S trimer-positive memory B cells for each patient. Insetnumbers indicate the absolute number and the percentage of Strimer-specific memory B cells isolated from each case.

FIGS. 23A-G show Genetic features of SARS-CoV-2-specific antibodyrepertoire. FIG. 23A shows that most of the 121 trimer S-specificantibodies are of IgG isotype. FIG. 23B shows the heavy chains The kappa(FIG. 23C) and lambda (FIG. 23D) light chains are comparably used.Compared to IgG repertoires of healthy human donors, IGHV3-30 andIGKV3-20 genes are over-represented in heavy and light chainrepertoires, respectively (β2-test, p<0.05). FIG. 23E shows that theusage of IGHJ6 gene was significantly higher in antigen-specificantibodies (β2-test, p<0.05). FIG. 23F shows that the CDRH3 length ofantigen-specific antibodies is significantly longer than in healthydonors (Kolmogorov-Smirnov test, p=0.014). FIG. 23G shows that for bothheavy and light chains, the V region nucleotide somatic hypermutationlevels are significantly lower than in antibodies of healthy donors(Kolmogorov-Smirnov test, p<0.001).

FIG. 24 shows The best-fit pseudovirus neutralization curves for 130samples that were positive in at least one of the screens shown in FIGS.15B-E. The 18 transfection supernatants that showed evidently betterpotency are highlighted in colors, while others with non-neutralizing orweakly neutralizing activities are shown in grey. One additionalsupernatant (Patient 1) that was initially missed in the pseudovirusscreen but later found to be a potent neutralizing mAb (1-87) is alsohighlighted.

FIG. 25 shows The pseudovirus neutralization profiles for 12 purifiedmAbs that strongly bound the S trimer but with weak or novirus-neutralizing activities. The four mAbs with weak neutralizingactivities against SARS-CoV-2 pseudovirus are shown in sold lines, andthe remaining 8 non-neutralizing mAbs are shown in dashed lines.

FIGS. 26A-C shows monoclonal Ab 2-43 bound to S trimer expressed onExpi293 cell surface can be competed out by mAbs directed to RBD butonly minimally by mAbs to the NTD region. FIG. 26A shows results for2-43 and proteins. FIG. 26B shows results for NTD-directed mAbs. FIG.26C shows results for RBD-directed mAbs.

FIGS. 27A-F show Cryo-EM data processing for antibody 2-4 in complexwith the S trimer. FIG. 27A shows a representative micrograph and CTF ofthe micrograph. FIG. 27B shows a representative 2D class averages. FIG.27C shows a resolution of the consensus map with C3 symmetry ascalculated by 3DFSC. FIG. 27D shows the local resolution of the full mapas calculated by cryoSPARC at an FSC cutoff of 0.5. Representativedensity of the Fab 2-4 and RBD interface, showing CRR H3, L3, and L3(FIG. 27E), along with CDR H2 and the N-linked glycosylation at ASN58(FIG. 27F).

FIGS. 28A-E show Fab 2-4 binding. FIG. 28A shows Fab 2-4 bindinginterface with RBD. FIG. 28B shows positions of antibodies 2-4, S309⁸,and BD-23⁹ on the trimeric CoV-2 spike. FIG. 28C shows somatichypermutations found only in the antibody 2-4 heavy chain, shown inbrown. The mutation A60T creates an NxT sequence leading to N58glycosylation. FIG. 28D shows antibody 2-4 in complex with S trimer. CDRloops are indicated in colors, 751 and side chains are shown forinteracting residues. FIG. 28E shows antibody BD-23⁹ in complex with Strimer.

FIGS. 29A-F show Cryo-EM data processing for antibody 4-8 in complexwith the S trimer. FIG. 29A shows a representative micrograph and CTF ofthe micrograph. FIG. 29B shows a representative 2D class averages. FIG.29C shows resolution of the spike in the RBD down conformation incomplex with Fab 4-8. FIG. 29D shows resolution of the spike in the RBDup conformation in complex with Fab 4-8. FIG. 29E shows local resolutionof the spike in the RBD down conformation in complex with Fab 4-8 at anFSC cutoff of 0.5. Two thresholds are shown. FIG. 29F shows localresolution of the spike in the RBD up conformation in complex with Fab4-8 at an FSC cutoff of 0.5. Two thresholds are shown.

FIG. 30 shows 3D reconstructions of NTD-targeting neutralizing antibody4-8 in complex with the SARS-CoV-2 spike trimer with the 1-RBD-upconformation.

FIGS. 31A-D show Cryo-EM data processing for antibody 2-43 in complexwith the S trimer. FIG. 31A shows a representative micrograph and CTF ofthe micrograph. FIG. 31B shows representative 2D class averages. FIG.31C shows resolution of Fab 2-43 in complex with S trimer. FIG. 31Dshows the local resolution of the full map as calculated by cryoSPARC atan FSC cutoff of 0.5.

FIGS. 32A-B show monoclonal antibody 2-15mut. FIG. 32A shows virusneutralization with the 2-15mut antibody. FIG. 32B shows potency of the2-15mut antibody.

FIGS. 33A-B show select mutants of the 4-8 monoclonal antibody. FIG. 33Ashows neutralization with antibodies 4-8 (39/51) and 4-8(39/51/57). FIG.33B shows potency of antibodies 4-8 (39/51) and 4-8(39/51/57).

FIG. 34 shows IC₅₀ and IC₉₀ values of selected monoclonal antibodymutants.

FIG. 35 shows that antibody 2-36 is a potent neutralizer againstSARS-CoV pseudovirus.

FIGS. 36A-B show ELISA binding of antibody 2-36 to SARS-CoV-2 Spiketrimer (FIG. 36A) and SARS-CoV Spike trimer (FIG. 36B). Antibody CR3022,an antibody previously reported to have cross-activity, served as acontrol.

FIGS. 37A-D show the binding affinities of antibody 2-36 and antibody2-4 to SARS-CoV-2 Spike trimer and to SARS-CoV Spike trimer, as measuredby SPR. Antibody 2-36 was confirmed to binds to both SARS-CoV-2 (FIG.37A) and SARS-CoV (FIG. 37B) spikes, but with a higher affinity toSARS-CoV-2 spike. As a control, the SARS-CoV-2 specific antibody 2-4only binds only to SARS-CoV-2 spike (FIG. 37C), but not to SARS-CoVspike (FIG. 37D).

FIGS. 38A-B show neutralization assay results. Antibody 2-36 neutralizedboth SARS-CoV-2 (FIG. 38A) and SARS-CoV (FIG. 38B), as compared to thecontrol antibody CR3022 that neutralized SARS-CoV (FIG. 38B) but onlyvery weakly neutralized SARS-CoV-2 (FIG. 38A); and as compared to theSARS-CoV-2 specific antibody 2-4 that only neutralize SARS-CoV-2 (FIG.38A).

FIGS. 39A-B show that antibody 2-36 neutralizes SARS-like coronavirusesusing hACE2. FIG. 39A shows the lineage of coronavirus, includingseveral from bats and pangolins. FIG. 39B shows that antibody 2-36 couldneutralize SARS-CoV and SARS-CoV-2 and their related lineage viruses,but that antibody 2-36 could not neutralize MERS-CoV and 229E,indicating its breadth.

FIGS. 40A-D show the cryo-EM structure of antibody 2-36 complexed withSARS-CoV-2. FIG. 40A shows the cryo-EM structure of 2-36 in complex withSARS-CoV-2 Spike trimer and FIG. 40B further details how 2-36 interactswith spike at the CDR level.

FIG. 40C shows that antibody 2-36 binds to the side of the RBD and cancompete with ACE2 for RBD binding, although its epitope does not overlapthe ACE2-binding site. FIG. 40D depicts that the spike protein is highlyconserved.

FIG. 41 shows a schematic representation of an engineered bispecificantibody combining the binding specificity of two neutralizingantibodies into one.

FIG. 42 shows that the 2-17/1-57 bispecific antibody against SARS-CoV-2does not enhance potency compared to respective single arm counterpart.Ab X and Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 43 shows potent neutralization of bispecific antibody 2-17/2-7against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 44 shows potent neutralization of bispecific antibody 2-17/2-15against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neuralization Ab).

FIG. 45 shows potent neutralization of bispecific antibody 2-17/2-30against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 46 shows potent neutralization of bispecific antibody 2-17/4-20against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 47 shows potent neutralization of bispecific antibody 5-24/1-57against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 48 shows potent neutralization of bispecific antibody 5-24/2-15against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 49 shows bispecific antibody 5-24/4-20 against SARS-CoV-2 does notenhance potency (IC₅₀) compared to respective single arm counterpart. AbX and Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 50 shows potent neutralization of bispecific antibody 1-20/1-68against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 51 shows potent neutralization of bispecific antibody 1-20/2-17against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 52 shows potent neutralization of bispecific antibody 1-20/4-18against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neuralization Ab).

FIG. 53 shows potent neutralization of bispecific antibody 1-20/5-24against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab).

FIG. 54 shows potent neutralization against SARS-CoV-2. Bispecificantibodies with 2-17 as a component are more potent than the single armcontrol (2-17/A32, A32 is a control antibody which shows no activityagainst SARS-CoV-2), indicating both arms are contributing to theneutralization activity of the bispecific molecule.

FIG. 55 shows potent neutralization against SARS-CoV-2 with bispecificantibodies containing 5-24 as a component. In antibody 5-24/A32, A32 isa control antibody which shows no activity against SARS-CoV-2,indicating both arms are contributing to the neutralization activity ofthe bispecific molecule.

FIG. 56 shows potent neutralization against SARS-CoV-2 with bispecificantibodies containing 1-20 as a component. In antibody 1-20/A32, A32 isa control antibody which shows no activity against SARS-CoV-2),indicating both arms are contributing to the neutralization activity ofthe bispecific molecule.

FIGS. 57A-E show bispecific antibodies with 1-20 (RBD) as a parentalantibody. FIG. 57A shows virus neutralization with bispecific antibodies1-20/5-24, 1-20/4-18, 1-20/2-17, and 1-20/1-68. FIG. 57B shows virusneutralization with the bispecific antibody 1-20/5-24 compared tocontrol antibodies. FIG. 57C shows virus neutralization with thebispecific antibody 1-20/4-18 compared to control antibodies. FIG. 57Dshows virus neutralization with the bispecific antibody 1-20/2-17compared to control antibodies. FIG. 57E shows virus neutralization withthe bispecific antibody 1-20/1-68 compared to control antibodies.

FIG. 58 shows potencies of bispecific antibodies with 1-20 (RBD) as aparental antibody.

FIGS. 59A-G show bispecific antibodies with 2-17 (NTD) as a parentalantibody. FIG. 59A shows virus neutralization with bispecific antibodies2-17/2-7, 2-17/1-57, 2-36/2-17, 2-17/4-20, 2-17/2-30, and 2-17/2-15.FIG. 59B shows virus neutralization with the bispecific antibody2-17/2-7 compared to control antibodies. FIG. 59C shows virusneutralization with the bispecific antibody 2-17/1-57 compared tocontrol antibodies. FIG. 59D shows virus neutralization with thebispecific antibody 2-17/2-15 compared to control antibodies. FIG. 59Eshows virus neutralization with the bispecific antibody 2-17/4-20compared to control antibodies. FIG. 59F shows virus neutralization withthe bispecific antibody 2-17/2-30 compared to control antibodies. FIG.59G shows virus neutralization with the bispecific antibody 2-36/2-17compared to control antibodies.

FIG. 60 shows potencies of bispecific antibodies with 2-17 (NTD) as aparental antibody.

FIGS. 61A-D show bispecific antibodies with 5-24 (NTD) as a parentalantibody. FIG. 61A shows virus neutralization with bispecific antibodies5-24/4-20, 5-24/1-57, 5-24/2 15, and 1-20/5-24. FIG. 61B shows virusneutralization with the bispecific antibody 5-24/2-compared to controlantibodies. FIG. 61C shows virus neutralization with the bispecificantibody 5-24/1-57 compared to control antibodies. FIG. 61D shows virusneutralization with the bispecific antibody 5-24/4-20 compared tocontrol antibodies.

FIG. 62 shows potencies of bispecific antibodies with 5-24 (NTD) as aparental antibody.

FIGS. 63A-D show bispecific antibodies with 2-36 (RBD) as a parentalantibody. FIG. 63A shows virus neutralization with bispecific antibodies2-36/1-68, 2-36/4-18, and 2-36/2-17. FIG. 63B shows virus neutralizationwith the bispecific antibody 2-36/2-17 compared to control antibodies.FIG. 63C shows virus neutralization with the bispecific antibody2-36/1-68 compared to control antibodies. FIG. 63D shows virusneutralization with the bispecific antibody 2-36/4-18 compared tocontrol antibodies.

FIG. 64 shows potencies of bispecific antibodies with 2-36 (RBD) as aparental antibody.

FIGS. 65A-C show bispecific antibodies with 2-30 (RBD) as a parentalantibody. FIG. 65A shows virus neutralization with bispecific antibodies2-30/4-18 and 2-30/1-68. FIG. 65B shows virus neutralization with thebispecific antibody 2-30/1-68 compared to control antibodies. FIG. 65Cshows virus neutralization with the bispecific antibody 2-30/4-18compared to control antibodies.

FIG. 66 show potencies of bispecific antibodies with 2-30 (RBD) as aparental antibody.

FIGS. 67A-D show comparative evaluations of bispecific antibody2-17/2-7. FIG. 67A shows the potency of the 2-17/2-7 bispecific antibodyto antibodies where one arm resembles the individual parental componentof the bispecific antibody while the other arm is an irrelevant control.It also compares the potency of the bispecific antibody to thecombination of the two single arm IgG controls. FIG. 67B shows virusneutralization with a combination of the parental antibodies and each ofthe parental antibodies. FIG. 67C shows virus neutralization with thebispecific antibody 2-17/2-7 compared to a combination of the parentalantibodies. FIG. 67D shows potency of combination parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. As each monoclonal antibody has two identical armsand each bispecific antibody has only one arm for each monoclonalantibody, testing at half of the amount allows for the sameconcentration of each monoclonal antibody arm to be compared to thebispecific antibody and the monoclonal antibody combination.

FIGS. 68A-D show comparative evaluations of bispecific antibody1-20/4-18. FIG. 68A compares the potency of the 1-20/4-18 bispecificantibody to an antibody where one arm resembles the individual parentalcomponent of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 68Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 68C shows virus neutralizationwith the bispecific antibody 1-20/4-18 compared to a combination of theparental antibodies. FIG. 68D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody.

FIGS. 69A-D show comparative evaluations of bispecific antibody1-20/5-24. FIG. 69A compares the potency of the 1-20/5-24 bispecificantibody to an antibody where one arm resembles the individual parentalcomponent of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 69Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 69C shows virus neutralizationwith the bispecific antibody 1-20/5-24 compared to a combination of theparental antibodies. FIG. 69D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody.

FIGS. 70A-D show comparative evaluations of bispecific antibody2-17/4-20. FIG. 70A compares the potency of the 2-17/4-20 bispecificantibody to an antibody where one arm resembles the individual parentalcomponent of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 70Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 70C shows virus neutralizationwith the bispecific antibody 2-17/4-20 compared to a combination of theparental antibodies. FIG. 70D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody.

FIGS. 71A-B show in vitro potency of bispecific antibodies againstSARS-CoV-2 authentic virus, strain USA/WA1. FIG. 71A showsneutralization for ten bispecific antibodies with IC₉₀ concentrationsbetween 0.004 μg/ml and 0.025 μg/ml. FIG. 71B shows neutralization fornine bispecific antibodies with IC₉₀ concentrations between 0.026 μg/mland 0.046 μg/ml. Authentic virus is another usage term for “infectious”virus. The term can also refer to “live virus”. The USA/WA1 strain isthe first strain isolated in the United States and is provided by BEIresources.

FIG. 72 shows in vitro potency of bispecific antibodies presented fromsmallest to highest IC₉₀ concentration. Highlighted antibodies weretested with controls.

FIGS. 73A-B show in vitro potency of bispecific antibodies showing IC₉₀and IC₅₀ concentrations. FIG. 73A shows in vitro potency of bispecificantibodies showing IC₉₀ and IC₅₀ concentrations relative to a 0.05 μg/mlthreshold. FIG. 73B shows in vitro potency of bispecific antibodiesshowing IC₉₀ and IC₅₀ concentrations relative to a 0.01 μg/ml threshold.

FIGS. 74A-D show comparative evaluation of the bispecific antibody1-57/1-68. FIG. 74A shows virus neutralization with the bispecificantibody 1-57/1-68 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arm, wherein AbX is PGDM1400. FIG. 74B showsvirus neutralization with a combination of the parental antibodies andeach of the parental antibodies. FIG. 74C shows virus neutralizationwith the bispecific antibody 1-57/1-68 compared to a combination of theparental antibodies. FIG. 74D shows potency of the bispecific antibody1-57/1-68 and a mix of each parental monoclonal antibodies tested eachat half of the amount of the corresponding bispecific antibody. Thecomparative data are from a single experiment, while, the data in thesummary table are averaged from multiple repeats.

FIGS. 75A-D show comparative evaluation of the bispecific antibody2-17/2-7. FIG. 75A shows virus neutralization with the bispecificantibody 2-17/2-7 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX and AbYare irrelevant control antibody arms, wherein AbX is PGDM1400 and AbY isA32. FIG. 75B shows virus neutralization with a combination of theparental antibodies and each of the parental antibodies. FIG. 75C showsvirus neutralization with the bispecific antibody 2-17/2-7 compared to acombination of the parental antibodies. FIG. 75D shows potency of thebispecific antibody 2-17/2-7 and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The comparative data are from a single experiment,while, the data in the summary table are averaged from multiple repeats.

FIGS. 76A-D show comparative evaluation of the bispecific antibody1-20/4-18. FIG. 76A shows virus neutralization with the bispecificantibody 1-20/4-18 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX and AbYare irrelevant control antibody arms, wherein AbX is PGDM1400 and AbY isA32. FIG. 76B shows virus neutralization with a combination of theparental antibodies and each of the parental antibodies. FIG. 76C showsvirus neutralization with the bispecific antibody 1-20/4-18 compared toa combination of the parental antibodies. FIG. 76D shows potency of thebispecific antibody 1-20/4-18 and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The comparative data are from a single experiment,while, the data in the summary table are averaged from multiple repeats.

FIGS. 77A-D show comparative evaluation of the bispecific antibody1-20/5-24. FIG. 77A shows virus neutralization with the bispecificantibody 1-20/5-24 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX and AbYare irrelevant control antibody arms, wherein AbX is PGDM1400 and AbY isA32. FIG. 77B shows virus neutralization with a combination of theparental antibodies and each of the parental antibodies. FIG. 77C showsvirus neutralization with the bispecific antibody 1-20/5-24 compared toa combination of the parental antibodies. FIG. 77D shows potency of thebispecific antibody 1-20/5-24 and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The comparative data are from a single experiment,while, the data in the summary table are averaged from multiple repeats.

FIGS. 78A-D show comparative evaluation of the bispecific antibody2-30/1-68. FIG. 78A shows virus neutralization with the bispecificantibody 2-30/1-68 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arms, wherein AbX is PGDM1400. FIG. 78Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 78C shows virus neutralizationwith the bispecific antibody 2-30/1-68 compared to a combination of theparental antibodies. FIG. 78D shows potency of the bispecific antibody2-30/1-68 and a mix of each parental monoclonal antibodies tested eachat half of the amount of the corresponding bispecific antibody. Thecomparative data are from a single experiment, while, the data in thesummary table are averaged from multiple repeats.

FIGS. 79A-D show comparative evaluation of the bispecific antibody2-7/4-8 (39/51). FIG. 79A shows virus neutralization with the bispecificantibody 2-7/4-8 (39/51) compared to two control bispecific antibodies,each comprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arms, wherein AbX is PGDM1400. FIG. 79Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 79C shows virus neutralizationwith the bispecific antibody 2-7/4-8 (39/51) compared to a combinationof the parental antibodies. FIG. 79D shows potency of the bispecificantibody 2-7/4-8 (39/51) and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The comparative data are from a single experiment,while, the data in the summary table are averaged from multiple repeats.

FIGS. 80A-D show comparative evaluation of the bispecific antibody1-57/1-87. FIG. 80A shows virus neutralization with the bispecificantibody 1-57/1-87 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arms, wherein AbX is PGDM1400. FIG. 80Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 80C shows virus neutralizationwith the bispecific antibody 1-57/1-87 compared to a combination of theparental antibodies. FIG. 80D shows potency of the bispecific antibody1-57/1-87 and a mix of each parental monoclonal antibodies tested eachat half of the amount of the corresponding bispecific antibody. Thecomparative data are from a single experiment, while, the data in thesummary table are averaged from multiple repeats.

FIG. 81 shows potency of additional bispecific antibodies.

FIGS. 82A-B show neutralizing activities of engineered bispecificantibodies. FIG. 82A shows neutralizing activities against wild-typevirus (WA1) at various antibody concentrations for bispecific antibodies2-17/2-7, 1-57/5-7, 5-7/1-57, 2-7/5-7, 5-7/2-7. FIG. 82B shows antibodypotency (IC₅₀ and IC₉₀) against wild-type virus (WA1) for bispecificantibodies 2-17/2-7, 1-57/5-7, 5-7/1-57, 2-7/5-7, 5-7/2-7.

FIGS. 83A-B show 2-7/5-7 bispecific antibody and parental antibodiesactivities. FIG. 83A shows neutralizing activities against wild-typevirus (WA1) at various antibody concentrations for bispecific antibody2-7/5-7, parental antibodies 2-7, 5-7, and a combination of 2-7 and 5-7parental antibodies. FIG. 83B shows IC₅₀ concentrations for bispecificantibody 2-7/5-7, parental antibodies 2-7, 5-7, and a combination of 2-7and 5-7 parental antibodies.

FIGS. 84A-B show activities of bispecific antibody 2-7/5-7 againstSARS-CoV-2 wild-type (WA1) and variant strains B1.1.7 (UK), B1.526 (NewYork), B1.351 (South Africa) and P.1 (Brazil). FIG. 84A showsneutralization activity of bispecific antibody 2-7/5-7 against variousSARS-CoV-2 strains at different antibody concentrations. FIG. 84B showsIC₅₀ and IC₉₀ concentrations for bispecific antibody 2-7/5-7 againstvarious SARS-CoV-2 strains.

FIGS. 85A-D show neutralization of pseudoviruses having mutationsassociated with SARS-CoV-2 variants with the bispecific 2-7/5-7antibody. FIG. 85A shows antibody neutralization curves againstcirculating SARS-CoV-2 virus variants. FIG. 85B shows antibody potencyagainst circulating SARS-CoV-2 virus variants. FIG. 85C shows antibodyneutralization curves against SARS-CoV-2 variants with high frequencymutations. FIG. shows antibody potency against SARS-CoV-2 variants withhigh frequency mutations.

FIGS. 86A-F show neutralization of pseudoviruses with SARS-CoV-2mutations corresponding to “variants of concern” using the bispecificantibody 2-7/5-7. FIG. 86A shows antibody neutralization curves againstB.1.1.7 (UK virus variant) with NTD mutations.

FIG. 86B shows antibody potency against B.1.1.7 (UK virus variant) withNTD mutations.

FIG. 86C shows antibody neutralization curves against B.1.352 (SA) virusvariant with NTD mutations. FIG. 86D shows antibody potency againstB.1.352 (SA) virus variant with NTD mutations. FIG. 86E shows antibodyneutralization curves against P.1 (BZ) virus variant with NTD mutations.FIG. 86F shows antibody potency against P.1 (BZ) virus variant with NTDmutations.

FIGS. 87A-F show neutralization of pseudoviruses with SARS-CoV-2mutations corresponding to “variants of interest” using the bispecificantibody 2-7/5-7. FIG. 87A shows antibody neutralization curves againstB.1.427 (CA) virus variant with NTD mutations. FIG. 87B shows antibodypotency against B.1.427 (CA) virus variant with NTD mutations. FIG. 87Cshows antibody neutralization curves against B.1.526 (NY) variant withNTD mutations. FIG. 87D shows antibody potency against B.1.526 (NY)variant with NTD mutations. FIG. 87E show antibody neuralization curvesagainst NJ variant with NTD mutations. FIG. 87F show antibody potencyagainst NJ variant with NTD mutations.

FIG. 88 shows summary of bispecific antibody 2-7/5-7 activity againstvariants. IC₅₀ is shown in circles. IC₉₀ is shown in squares.

FIGS. 89A-C shows neutralization activity of bispecific antibody 2-7/5-7and parental 2-7 and 5-7 monoclonal antibodies against SARS-CoV-2variants (live viruses). FIG. 89A shows the neutralization curve forbispecific antibody 2-7/5-7. FIG. 89B shows the neutralization curve forparental antibody 2-7. FIG. 89C shows the neutralization curve forparental antibody 5-7.

FIGS. 90A-D show virus neutralization with monoclonal antibody 2-36.FIG. 90A shows screening of transfection supernatant for neutralizationactivity against SARS-CoV-2 pseudovirus. FIG. 90B shows screening oftransfection supernatant for neutralization activity against SARS-CoVpseudovirus. FIG. 90C shows 2-36 neutralization IC₅₀ (μg/mL) againstSARS-CoV-2 pseudovirus (PV) and live virus (LV). FIG. 90D shows 2-36neutralization IC₅₀ (μg/mL) against SARS-CoV pseudovirus (PV) and livevirus (LV).

FIGS. 91A-B show binding of monoclonal antibody 2-36 to SARS-CoV-2 (FIG.91A) and SARS-CoV (FIG. 91B) spike as determined by ELISA.

FIGS. 92A-H show binding affinity for monoclonal antibodies 2-36 and 2-4to SARS-CoV-2 and SARS-CoV viruses as measured by SPR. FIG. 92A shows2-36 binding affinity to SARS-CoV-2 spike protein. FIG. 92B shows 2-4binding affinity to SARS-CoV-2 spike protein. FIG. 92C shows 2-36binding affinity to SARS-CoV spike protein. FIG. 92D shows 2-4 bindingaffinity to SARS-CoV spike protein. FIG. 92E shows 2-36 binding affinityto SARS-CoV-2 receptor binding domain (RBD). FIG. 92F shows 2-4 bindingaffinity to SARS-CoV-2 RBD. FIG. 92G shows 2-36 binding affinity toSARS-CoV RBD. FIG. 92H shows 2-4 binding affinity to SARS-CoV RBD.

FIGS. 93A-B show binding to SARS-CoV-2 spike protein. FIG. 93A showsthat binding of monoclonal antibody 2-36 to SARS-CoV-2 spike isinhibited by CR3022. FIG. 93B shows that monoclonal antibody 2-36inhibits hACE2 binding to SARS-CoV-2 spike protein.

FIG. 94 shows conservation analysis on the RBD among SARS CoV-2, SARSCoV-1, Bat CoVs, and Human CoVs virus strains. The analysis shows thatthe 2-36 binding site is highly conserved; with regions of highconservation in grey and low conservation in red. The 2-36 binding siteis outlined in blue.

FIGS. 95A-D show that monoclonal antibody 2-36 neutralizes SARS-CoV-2variants and SARS-like coronaviruses using hACE2. FIG. 95A showsneutralization against live variants. FIG. 95B shows neutralizationagainst pseudovariants. FIG. 95C shows evolution tree of viruses. FIG.95D shows antibody potency against viruses.

FIGS. 96A-D shows that monoclonal antibody 2-36 neutralizes SARS-likecoronaviruses using hACE2. FIG. 96A shows virus neutralization with 2-36antibody. FIG. 96B shows virus neutralization with S309 antibody. FIG.96C shows virus neutralization with COVA1-16 antibody. FIG. 96D showsvirus neutralization with CR3022 antibody.

FIGS. 97A-D show in vitro selection of 2-36 antibody escape mutations.FIG. 97A shows evolution of escape mutations during in vitro passage ofSARS-CoV-2 USA/WA1 in Vero E6 cells in the presence of 2-36. FIG. 97Bshows 2-36 neutralization activity tested against virus passages. FIG.97C shows spike protein with selected mutation localized. FIG. 97D showsthat the selected escape mutations were introduced into pseudovirusesand then 2-36 neutralization activity was tested against these viruses.

DETAILED DESCRIPTION OF THE INVENTION Definitions

The following are definitions of terms used in the presentspecification. The initial definition provided for a group or termherein applies to that group or term throughout the presentspecification individually or as part of another group, unless otherwiseindicated. Unless otherwise defined, all technical and scientific termsused herein have the same meaning as commonly understood by one ofordinary skill in the art.

The singular forms “a”, “an” and “the” include plural reference unlessthe context clearly dictates otherwise. The use of the word “a” or “an”when used in conjunction with the term “comprising” in the claims and/orthe specification may mean “one,” but it is also consistent with themeaning of “one or more,” “at least one,” and “one or more than one.”

As used herein the term “about” is used herein to mean approximately,roughly, around, or in the region of When the term “about” is used inconjunction with a numerical range, it modifies that range by extendingthe boundaries above and below the numerical values set forth. Ingeneral, the term “about” is used herein to modify a numerical valueabove and below the stated value by a variance of 20 percent up or down(higher or lower).

As used herein, the term “subject” refers to a vertebrate animal. In oneembodiment, the subject is a mammal or a mammalian species. In oneembodiment, the subject is a human. In one embodiment, the subject is ahealthy human adult. In other embodiments, the subject is a non-humanvertebrate animal, including, without limitation, non-human primates,laboratory animals, livestock, racehorses, domesticated animals, andnon-domesticated animals. In one embodiment, the term “human subjects”means a population of healthy human adults.

As used herein, the term “patient” refers to a human or animal.

The term “mammal” includes, but is not limited to, a human, mouse, rat,guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as amonkey, chimpanzee, baboon or rhesus. In one embodiment, the mammal is ahuman.

As used herein, the term “therapeutically effective” includesprophylaxis, as well as treatment of a subject having suspected ofhaving a viral infection.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3of SEQ ID NO: 63. In some embodiments, the variable domain of the firstlight chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1,CDR2, and CDR3 of SEQ ID NO: 64. In some embodiments, the variabledomain of the second heavy chain comprises CDR1, CDR2, and CDR3 of SEQID NO: 61 or CDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments,the variable domain of the second light chain comprises CDR1, CDR2, andCDR3 SEQ ID NO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on an S protein of aSARS-CoV-2 particle.

In certain aspects, the invention provides a method of treating aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a composition comprising a bispecificmolecule, wherein the bispecific molecule comprises a first polypeptidechain and a second polypeptide chain, wherein: the first polypeptidechain comprises: a first light chain comprising a variable domain and aconstant domain; a first heavy chain comprising a variable domain and aconstant domain; the second polypeptide chain comprises: a second lightchain comprising a variable domain and a constant domain; and a secondheavy chain comprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66. In someembodiments, the variable domain of the first heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3 of SEQ IDNO: 63. In some embodiments, the variable domain of the first lightchain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1, CDR2, andCDR3 of SEQ ID NO: 64. In some embodiments, the variable domain of thesecond heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 61 orCDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments, the variabledomain of the second light chain comprises CDR1, CDR2, and CDR3 SEQ IDNO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a method of preventing aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a composition comprising a bispecificmolecule, wherein the bispecific molecule comprises a first polypeptidechain and a second polypeptide chain, wherein: the first polypeptidechain comprises: a first light chain comprising a variable domain and aconstant domain; a first heavy chain comprising a variable domain and aconstant domain; the second polypeptide chain comprises: a second lightchain comprising a variable domain and a constant domain; and a secondheavy chain comprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3of SEQ ID NO: 63. In some embodiments, the variable domain of the firstlight chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1,CDR2, and CDR3 of SEQ ID NO: 64. In some embodiments, the variabledomain of the second heavy chain comprises CDR1, CDR2, and CDR3 of SEQID NO: 61 or CDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments,the variable domain of the second light chain comprises CDR1, CDR2, andCDR3 SEQ ID NO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of asynthesized monoclonal antibody, or a functional fragment thereof,comprising a heavy chain having a variable domain and a constant domainand a light chain having a variable domain and a constant domain,wherein the antibody binds an antigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody neutralizes a coronavirus. In some embodiments, the coronavirusis SARS-CoV-2. In some embodiments, the antibody specifically binds anepitope on the surface of the coronavirus. In some embodiments, theepitope comprises at least a portion of a coronavirus spike protein. Insome embodiments, the at least a portion of a coronavirus spike proteincomprises a receptor binding domain (RBD) of a spike protein. In someembodiments, the coronavirus is a SARS-CoV-2 coronavirus. In someembodiments, the antibody is administered in combination with a secondpharmaceutical agent.

In certain aspects, the invention provides a method of preventing aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of asynthesized monoclonal antibody, or a functional fragment thereof,comprising a heavy chain having a variable domain and a constant domainand a light chain having a variable and a constant domain, wherein theantibody binds an antigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody neutralizes a coronavirus. In some embodiments, the coronavirusis SARS-CoV-2. In some embodiments, the antibody specifically binds anepitope on the surface of the coronavirus. In some embodiments, theepitope comprises at least a portion of a coronavirus spike protein. Insome embodiments, the at least a portion of a coronavirus spike proteincomprises a receptor binding domain (RBD) of a spike protein. In someembodiments, the coronavirus is a SARS-CoV-2 coronavirus. In someembodiments, the antibody is administered in combination with a secondpharmaceutical agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 7, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 9, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 11, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 33, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 39, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 4, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 8, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 10, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 12, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 26, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 30, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 40, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 4.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 7 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 8.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 9 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 10.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 11 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 12. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 17 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 19 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 21 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 25 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 29 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 30.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 33 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 37 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 38. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 39 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 40. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 43 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 45 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 3 and the light chain variable domain comprises SEQ ID NO: 4. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO: 7and the light chain variable domain comprises SEQ ID NO: 8. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 9 andthe light chain variable domain comprises SEQ ID NO: 10. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 11 andthe light chain variable domain comprises SEQ ID NO: 12. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 17 andthe light chain variable domain comprises SEQ ID NO: 18. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 19 andthe light chain variable domain comprises SEQ ID NO: 20. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 21 andthe light chain variable domain comprises SEQ ID NO: 22. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 25 andthe light chain variable domain comprises SEQ ID NO: 26. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 29 andthe light chain variable domain comprises SEQ ID NO: 30. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 31 andthe light chain variable domain comprises SEQ ID NO: 32. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 33 andthe light chain variable domain comprises SEQ ID NO: 34. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 37 andthe light chain variable domain comprises SEQ ID NO: 38. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 39 andthe light chain variable domain comprises SEQ ID NO: 40. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 43 andthe light chain variable domain comprises SEQ ID NO: 44. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 45 andthe light chain variable domain comprises SEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 3; the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 7; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 9; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 11; or the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 17. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:19; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 21; the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 25; the CDR1, CDR2, and CDR3 regions ofSEQ ID NO: 29; or the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 31. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 33; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 37; the CDR1, CDR2, and CDR3 regions of SEQ ID NO:39; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 43; or the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 45. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 4; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 8; the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 10; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 12; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 18. In some embodiments, the light chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 20; the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 22; the CDR1, CDR2, and CDR3 regions of SEQID NO: 26; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 30; or theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 32. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 34; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 38; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 40; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 44; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 46.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427.

In some embodiments, the antibody specifically binds an epitope on thesurface of the coronavirus. In some embodiments, the epitope comprisesat least a portion of a coronavirus spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises areceptor binding domain (RBD) of a spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises aN-Terminal domain (NTD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a synthesized monoclonal antibody, or a functional fragmentthereof, comprising a heavy chain having a variable domain and aconstant domain and a light chain having a variable domain and aconstant domain, wherein the antibody binds an antigen on a coronavirusparticle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 7, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 9, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 11, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 33, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 39, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 4, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 8, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 10, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 12, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 26, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 30, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 40, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 4.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 7 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 8.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 9 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 10.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 11 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 12. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 17 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 19 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 21 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 25 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 29 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 30. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 31 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 33 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 37 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 38.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 39 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 40. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 43 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 45 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 3 and the light chain variable domain comprises SEQ ID NO: 4. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO: 7and the light chain variable domain comprises SEQ ID NO: 8. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 9 andthe light chain variable domain comprises SEQ ID NO: 10. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 11 andthe light chain variable domain comprises SEQ ID NO: 12. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 17 andthe light chain variable domain comprises SEQ ID NO: 18. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 19 andthe light chain variable domain comprises SEQ ID NO: 20. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 21 andthe light chain variable domain comprises SEQ ID NO: 22. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 25 andthe light chain variable domain comprises SEQ ID NO: 26. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 29 andthe light chain variable domain comprises SEQ ID NO: 30. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 31 andthe light chain variable domain comprises SEQ ID NO: 32. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 33 andthe light chain variable domain comprises SEQ ID NO: 34. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 37 andthe light chain variable domain comprises SEQ ID NO: 38. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 39 andthe light chain variable domain comprises SEQ ID NO: 40. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 43 andthe light chain variable domain comprises SEQ ID NO: 44. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 45 andthe light chain variable domain comprises SEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 3; the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 7; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 9; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 11; or the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 17. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:19; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 21; the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 25; the CDR1, CDR2, and CDR3 regions ofSEQ ID NO: 29; or the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 31. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 33; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 37; the CDR1, CDR2, and CDR3 regions of SEQ ID NO:39; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 43; or the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 45. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 4; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 8; the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 10; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 12; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 18. In some embodiments, the light chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 20; the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 22; the CDR1, CDR2, and CDR3 regions of SEQID NO: 26; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 30; or theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 32. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 34; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 38; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 40; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 44; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 46.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427.

In some embodiments, the antibody specifically binds an epitope on thesurface of the coronavirus. In some embodiments, the epitope comprisesat least a portion of a coronavirus spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises areceptor binding domain (RBD) of a spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises aN-Terminal domain (NTD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus. In some embodiments, thecomposition is administered in combination with a second therapeuticagent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 51, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 55, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 67, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 71, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 75, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 79, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 83, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 87, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 91, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 95, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 99, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 103, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 107, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 115, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 119, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 123, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 127,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 131, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 139, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 143, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 147,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 151, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 155, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 159, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 163,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 167, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 171, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 175, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 179,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:183.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 52,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 56, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 68; a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 72, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 76, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 80, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 84, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 88, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 92, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 96, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 100, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 104, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 108,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 116, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 120, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 124, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 128,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 132, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 140, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 144, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 148,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 152, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 156, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 160, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 164,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 168, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 172, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 176, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 180,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:184.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 53,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 57, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 69, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 73, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 77, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 81, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 85, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 89, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 93, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 97, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 101, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 105, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 109,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 117, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 121, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 125, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 129,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 133, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 141, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 145, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 149,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 153, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 157, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 161, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 165,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 169, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 173, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 177, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 181,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 185.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 54,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 58, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 70, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 74, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 78, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 82, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 86, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 90, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 94, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 98, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 102, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 106, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 110,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 118, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 122, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 126, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 130,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 134, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 142, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 146, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 150,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 154, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 158, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 162, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 166,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 170, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 174, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 178, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 182,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 186.

In some embodiments, variable domain of the first heavy chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 35, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 25, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 19, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 41.

In some embodiments, variable domain of the first light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 28, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 36, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 26, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 20, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 6, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 42.

In some embodiments, variable domain of the second heavy chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 27, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 5, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 19, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 21, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 29, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 35, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 23, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 25, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 37, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 39, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 43, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 9.

In some embodiments, variable domain of the second light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 6, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 30, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 26, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 40, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 10.

In some embodiments, the variable domain of the first heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 51; the CDR1, CDR2, andCDR3 of SEQ ID NO: the CDR1, CDR2, and CDR3 of SEQ ID NO: 67; the CDR1,CDR2, and CDR3 of SEQ ID NO: 71; the CDR1, CDR2, and CDR3 of SEQ ID NO:75; the CDR1, CDR2, and CDR3 of SEQ ID NO: 79; the CDR1, CDR2, and CDR3of SEQ ID NO: 83; the CDR1, CDR2, and CDR3 of SEQ ID NO: 87; the CDR1,CDR2, and CDR3 of SEQ ID NO: 91; the CDR1, CDR2, and CDR3 of SEQ ID NO:95; the CDR1, CDR2, and CDR3 of SEQ ID NO: 99; the CDR1, CDR2, and CDR3of SEQ ID NO: 103; the CDR1, CDR2, and CDR3 of SEQ ID NO: 107; the CDR1,CDR2, and CDR3 of SEQ ID NO: 115; the CDR1, CDR2, and CDR3 of SEQ ID NO:119, the CDR1, CDR2, and CDR3 of SEQ ID NO: 123, the CDR1, CDR2, andCDR3 of SEQ ID NO: 127; the CDR1, CDR2, and CDR3 of SEQ ID NO: 131; theCDR1, CDR2, and CDR3 of SEQ ID NO: 139; the CDR1, CDR2, and CDR3 of SEQID NO: 143; the CDR1, CDR2, and CDR3 of SEQ ID NO: 147; the CDR1, CDR2,and CDR3 of SEQ ID NO: 151; the CDR1, CDR2, and CDR3 of SEQ ID NO: 155;the CDR1, CDR2, and CDR3 of SEQ ID NO: 159; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 163; the CDR1, CDR2, and CDR3 of SEQ ID NO: 167, the CDR1,CDR2, and CDR3 of SEQ ID NO: 171, the CDR1, CDR2, and CDR3 of SEQ ID NO:175, the CDR1, CDR2, and CDR3 of SEQ ID NO: 179, or the CDR1, CDR2, andCDR3 of SEQ ID NO: 183.

In some embodiments, the variable domain of the first light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 52; the CDR1, CDR2, andCDR3 of SEQ ID NO: 56; the CDR1, CDR2, and CDR3 of SEQ ID NO: 68; theCDR1, CDR2, and CDR3 of SEQ ID NO: 72; the CDR1, CDR2, and CDR3 of SEQID NO: 76; the CDR1, CDR2, and CDR3 of SEQ ID NO: 80; the CDR1, CDR2,and CDR3 of SEQ ID NO: 84; the CDR1, CDR2, and CDR3 of SEQ ID NO: 88;the CDR1, CDR2, and CDR3 of SEQ ID NO: 92; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 96; the CDR1, CDR2, and CDR3 of SEQ ID NO: 100; the CDR1,CDR2, and CDR3 of SEQ ID NO: 104; the CDR1, CDR2, and CDR3 of SEQ ID NO:108; the CDR1, CDR2, and CDR3 of SEQ ID NO: 116; the CDR1, CDR2, andCDR3 of SEQ ID NO: 120; the CDR1, CDR2, and CDR3 of SEQ ID NO: 124; theCDR1, CDR2, and CDR3 of SEQ ID NO: 128; the CDR1, CDR2, and CDR3 of SEQID NO: 132; the CDR1, CDR2, and CDR3 of SEQ ID NO: 140; the CDR1, CDR2,and CDR3 of SEQ ID NO: 144; the CDR1, CDR2, and CDR3 of SEQ ID NO: 148;the CDR1, CDR2, and CDR3 of SEQ ID NO: 152; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 156; the CDR1, CDR2, and CDR3 of SEQ ID NO: 160; the CDR1,CDR2, and CDR3 of SEQ ID NO: 164; the CDR1, CDR2, and CDR3 of SEQ ID NO:168, the CDR1, CDR2, and CDR3 of SEQ ID NO: 172, the CDR1, CDR2, andCDR3 of SEQ ID NO: 176, the CDR1, CDR2, and CDR3 of SEQ ID NO: 180, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 184.

In some embodiments, the variable domain of the second heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 53; the CDR1, CDR2, andCDR3 of SEQ ID NO: 57; the CDR1, CDR2, and CDR3 of SEQ ID NO: 69; theCDR1, CDR2, and CDR3 of SEQ ID NO: 73; the CDR1, CDR2, and CDR3 of SEQID NO: 77; the CDR1, CDR2, and CDR3 of SEQ ID NO: 81; the CDR1, CDR2,and CDR3 of SEQ ID NO: 85; the CDR1, CDR2, and CDR3 of SEQ ID NO: 89;the CDR1, CDR2, and CDR3 of SEQ ID NO: 93; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 97; the CDR1, CDR2, and CDR3 of SEQ ID NO: 101; the CDR1,CDR2, and CDR3 of SEQ ID NO: 105; the CDR1, CDR2, and CDR3 of SEQ ID NO:109; the CDR1, CDR2, and CDR3 of SEQ ID NO: 117; the CDR1, CDR2, andCDR3 of SEQ ID NO: 121; the CDR1, CDR2, and CDR3 of SEQ ID NO: 125; theCDR1, CDR2, and CDR3 of SEQ ID NO: 129; the CDR1, CDR2, and CDR3 of SEQID NO: 133; the CDR1, CDR2, and CDR3 of SEQ ID NO: 141; the CDR1, CDR2,and CDR3 of SEQ ID NO: 145; the CDR1, CDR2, and CDR3 of SEQ ID NO: 149;the CDR1, CDR2, and CDR3 of SEQ ID NO: 153; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 157; the CDR1, CDR2, and CDR3 of SEQ ID NO: 161; the CDR1,CDR2, and CDR3 of SEQ ID NO: 165; the CDR1, CDR2, and CDR3 of SEQ ID NO:169, the CDR1, CDR2, and CDR3 of SEQ ID NO: 173, the CDR1, CDR2, andCDR3 of SEQ ID NO: 177, the CDR1, CDR2, and CDR3 of SEQ ID NO: 181, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 185.

In some embodiments, the variable domain of the second light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 54; the CDR1, CDR2, andCDR3 of SEQ ID NO: 58; the CDR1, CDR2, and CDR3 of SEQ ID NO: 70; theCDR1, CDR2, and CDR3 of SEQ ID NO: 74; the CDR1, CDR2, and CDR3 of SEQID NO: 78; the CDR1, CDR2, and CDR3 of SEQ ID NO: 82; the CDR1, CDR2,and CDR3 of SEQ ID NO: 86; the CDR1, CDR2, and CDR3 of SEQ ID NO: 90;the CDR1, CDR2, and CDR3 of SEQ ID NO: 94; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 98; the CDR1, CDR2, and CDR3 of SEQ ID NO: 102; the CDR1,CDR2, and CDR3 of SEQ ID NO: 106; the CDR1, CDR2, and CDR3 of SEQ ID NO:110; the CDR1, CDR2, and CDR3 of SEQ ID NO: 118; the CDR1, CDR2, andCDR3 of SEQ ID NO: 122; the CDR1, CDR2, and CDR3 of SEQ ID NO: 126; theCDR1, CDR2, and CDR3 of SEQ ID NO: 130; the CDR1, CDR2, and CDR3 of SEQID NO: 134; the CDR1, CDR2, and CDR3 of SEQ ID NO: 142; the CDR1, CDR2,and CDR3 of SEQ ID NO: 146; the CDR1, CDR2, and CDR3 of SEQ ID NO: 150;the CDR1, CDR2, and CDR3 of SEQ ID NO: 154; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 158; the CDR1, CDR2, and CDR3 of SEQ ID NO: 162, the CDR1,CDR2, and CDR3 of SEQ ID NO: 166; the CDR1, CDR2, and CDR3 of SEQ ID NO:170, the CDR1, CDR2, and CDR3 of SEQ ID NO: 174, the CDR1, CDR2, andCDR3 of SEQ ID NO: 178, the CDR1, CDR2, and CDR3 of SEQ ID NO: 182, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 186.

In some embodiments, the molecule comprises SEQ ID NO: 51, SEQ ID NO:52, SEQ ID NO: 53, and SEQ ID NO: 54. In some embodiments, the moleculecomprises SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO:58. In some embodiments, the molecule comprises SEQ ID NO: 67, SEQ IDNO: 68, SEQ ID NO: 69, and SEQ ID NO: In some embodiments, the moleculecomprises SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO:74. In some embodiments, the molecule comprises SEQ ID NO: SEQ ID NO:76, SEQ ID NO: 77, and SEQ ID NO: 78. In some embodiments, the moleculecomprises SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO:82. In some embodiments, the molecule comprises SEQ ID NO: 83, SEQ IDNO: 84, SEQ ID NO: 85, and SEQ ID NO: 86. In some embodiments, themolecule comprises SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, and SEQID NO: 90. In some embodiments, the molecule comprises SEQ ID NO: 91,SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94. In some embodiments,the molecule comprises SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, andSEQ ID NO: 98. In some embodiments, the molecule comprises SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. In someembodiments, the molecule comprises SEQ ID NO: 103, SEQ ID NO: 104, SEQID NO: 105, and SEQ ID NO: 106. In some embodiments, the moleculecomprises SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, and SEQ ID NO:110. In some embodiments, the molecule comprises SEQ ID NO: 115, SEQ IDNO: 116, SEQ ID NO: 117, and SEQ ID NO: 118. In some embodiments, themolecule comprises SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, andSEQ ID NO: 122.

In some embodiments, the molecule comprises SEQ ID NO: 123, SEQ ID NO:124, SEQ ID NO: 125, and SEQ ID NO: 126. In some embodiments, themolecule comprises SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, andSEQ ID NO: 130. In some embodiments, the molecule comprises SEQ ID NO:131, SEQ ID NO: 132, SEQ ID NO: 133, and SEQ ID NO: 133. In someembodiments, the molecule comprises SEQ ID NO: 139, SEQ ID NO: 140, SEQID NO: 141, and SEQ ID NO: 142. In some embodiments, the moleculecomprises SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO:146. In some embodiments, the molecule comprises SEQ ID NO: 147, SEQ IDNO: 148, SEQ ID NO: 149, and SEQ ID NO: 150. In some embodiments, themolecule comprises SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, andSEQ ID NO: 154. In some embodiments, the molecule comprises SEQ ID NO:155, SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158. In someembodiments, the molecule comprises SEQ ID NO: 159, SEQ ID NO: 160, SEQID NO: 161, and SEQ ID NO: 162. In some embodiments, the moleculecomprises SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO:166. In some embodiments, the molecule comprises SEQ ID NO: 167, SEQ IDNO: 168, SEQ ID NO: 169, and SEQ ID NO: 170. In some embodiments, themolecule comprises SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, andSEQ ID NO: 174. In some embodiments, the molecule comprises SEQ ID NO:175, SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178. In someembodiments, the molecule comprises SEQ ID NO: 179, SEQ ID NO: 180, SEQID NO: 181, and SEQ ID NO: 182. In some embodiments, the moleculecomprises SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO:186.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427.

In some embodiments, the molecule specifically recognizes a firstepitope and a second epitope on a SARS-CoV-2 particle. In someembodiments, the first epitope comprises at least a portion of areceptor binding domain (RBD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the second epitope comprises at least aportion of a N-terminal domain (NTD) on a spike protein of a SARS-CoV-2particle.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a composition comprising abispecific molecule comprising a first polypeptide chain and a secondpolypeptide chain, wherein: the first polypeptide chain comprises: afirst light chain comprising a variable domain and a constant domain; afirst heavy chain comprising a variable domain and a constant domain;the second polypeptide chain comprises: a second light chain comprisinga variable domain and a constant domain; and a second heavy chaincomprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 51, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 55, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 67, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 71, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 75, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 79, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 83, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 87, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 91, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 95, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 99, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 103, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 107, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 115, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 119, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 123, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 127,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 131, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 139, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 143, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 147,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 151, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 155, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 159, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 163,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 167, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 171, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 175, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 179,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:183.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 52,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 56, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 68; a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 72, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 76, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 80, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 84, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 88, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 92, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 96, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 100, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 104, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 108,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 116, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 120, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 124, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 128,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 132, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 140, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 144, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 148,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 152, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 156, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 160, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 164,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 168, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 172, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 176, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 180,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:184.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 53,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 57, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 69, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 73, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 77, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 81, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 85, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 89, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 93, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 97, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 101, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 105, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 109,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 117, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 121, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 125, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 129,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 133, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 141, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 145, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 149,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 153, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 157, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 161, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 165,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 169, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 173, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 177, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 181,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 185.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 54,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 58, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 70, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 74, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 78, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 82, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 86, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 90, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 94, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 98, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 102, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 106, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 110,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 118, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 122, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 126, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 130,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 134, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 142, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 146, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 150,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 154, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 158, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 162, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 166,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 170, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 174, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 178, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 182,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 186.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 35, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 25, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 17, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 37, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 19, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 13, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 5, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 21, or a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 41.

In some embodiments, the variable domain of the first light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 28, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 18, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 6, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 22, or a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 42.

In some embodiments, the variable domain of the second heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 15, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 5, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 15, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 35, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 23, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 37, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 39, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 43, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 9.

In some embodiments, variable domain of the second light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 6, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 30, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 26, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 40, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 10.

In some embodiments, the variable domain of the first heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 51; the CDR1, CDR2, andCDR3 of SEQ ID NO: the CDR1, CDR2, and CDR3 of SEQ ID NO: 67; the CDR1,CDR2, and CDR3 of SEQ ID NO: 71; the CDR1, CDR2, and CDR3 of SEQ ID NO:75; the CDR1, CDR2, and CDR3 of SEQ ID NO: 79; the CDR1, CDR2, and CDR3of SEQ ID NO: 83; the CDR1, CDR2, and CDR3 of SEQ ID NO: 87; the CDR1,CDR2, and CDR3 of SEQ ID NO: 91; the CDR1, CDR2, and CDR3 of SEQ ID NO:95; the CDR1, CDR2, and CDR3 of SEQ ID NO: 99; the CDR1, CDR2, and CDR3of SEQ ID NO: 103; the CDR1, CDR2, and CDR3 of SEQ ID NO: 107; the CDR1,CDR2, and CDR3 of SEQ ID NO: 115; the CDR1, CDR2, and CDR3 of SEQ ID NO:119, the CDR1, CDR2, and CDR3 of SEQ ID NO: 123, the CDR1, CDR2, andCDR3 of SEQ ID NO: 127; the CDR1, CDR2, and CDR3 of SEQ ID NO: 131; theCDR1, CDR2, and CDR3 of SEQ ID NO: 139; the CDR1, CDR2, and CDR3 of SEQID NO: 143; the CDR1, CDR2, and CDR3 of SEQ ID NO: 147; the CDR1, CDR2,and CDR3 of SEQ ID NO: 151; the CDR1, CDR2, and CDR3 of SEQ ID NO: 155;the CDR1, CDR2, and CDR3 of SEQ ID NO: 159; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 163; the CDR1, CDR2, and CDR3 of SEQ ID NO: 167, the CDR1,CDR2, and CDR3 of SEQ ID NO: 171, the CDR1, CDR2, and CDR3 of SEQ ID NO:175, the CDR1, CDR2, and CDR3 of SEQ ID NO: 179, or the CDR1, CDR2, andCDR3 of SEQ ID NO: 183.

In some embodiments, the variable domain of the first light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 52; the CDR1, CDR2, andCDR3 of SEQ ID NO: 56; the CDR1, CDR2, and CDR3 of SEQ ID NO: 68; theCDR1, CDR2, and CDR3 of SEQ ID NO: 72; the CDR1, CDR2, and CDR3 of SEQID NO: 76; the CDR1, CDR2, and CDR3 of SEQ ID NO: 80; the CDR1, CDR2,and CDR3 of SEQ ID NO: 84; the CDR1, CDR2, and CDR3 of SEQ ID NO: 88;the CDR1, CDR2, and CDR3 of SEQ ID NO: 92; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 96; the CDR1, CDR2, and CDR3 of SEQ ID NO: 100; the CDR1,CDR2, and CDR3 of SEQ ID NO: 104; the CDR1, CDR2, and CDR3 of SEQ ID NO:108; the CDR1, CDR2, and CDR3 of SEQ ID NO: 116; the CDR1, CDR2, andCDR3 of SEQ ID NO: 120; the CDR1, CDR2, and CDR3 of SEQ ID NO: 124; theCDR1, CDR2, and CDR3 of SEQ ID NO: 128; the CDR1, CDR2, and CDR3 of SEQID NO: 132; the CDR1, CDR2, and CDR3 of SEQ ID NO: 140; the CDR1, CDR2,and CDR3 of SEQ ID NO: 144; the CDR1, CDR2, and CDR3 of SEQ ID NO: 148;the CDR1, CDR2, and CDR3 of SEQ ID NO: 152; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 156; the CDR1, CDR2, and CDR3 of SEQ ID NO: 160; the CDR1,CDR2, and CDR3 of SEQ ID NO: 164; the CDR1, CDR2, and CDR3 of SEQ ID NO:168, the CDR1, CDR2, and CDR3 of SEQ ID NO: 172, the CDR1, CDR2, andCDR3 of SEQ ID NO: 176, the CDR1, CDR2, and CDR3 of SEQ ID NO: 180, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 184.

In some embodiments, the variable domain of the second heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 53; the CDR1, CDR2, andCDR3 of SEQ ID NO: 57; the CDR1, CDR2, and CDR3 of SEQ ID NO: 69; theCDR1, CDR2, and CDR3 of SEQ ID NO: 73; the CDR1, CDR2, and CDR3 of SEQID NO: 77; the CDR1, CDR2, and CDR3 of SEQ ID NO: 81; the CDR1, CDR2,and CDR3 of SEQ ID NO: 85; the CDR1, CDR2, and CDR3 of SEQ ID NO: 89;the CDR1, CDR2, and CDR3 of SEQ ID NO: 93; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 97; the CDR1, CDR2, and CDR3 of SEQ ID NO: 101; the CDR1,CDR2, and CDR3 of SEQ ID NO: 105; the CDR1, CDR2, and CDR3 of SEQ ID NO:109; the CDR1, CDR2, and CDR3 of SEQ ID NO: 117; the CDR1, CDR2, andCDR3 of SEQ ID NO: 121; the CDR1, CDR2, and CDR3 of SEQ ID NO: 125; theCDR1, CDR2, and CDR3 of SEQ ID NO: 129; the CDR1, CDR2, and CDR3 of SEQID NO: 133; the CDR1, CDR2, and CDR3 of SEQ ID NO: 141; the CDR1, CDR2,and CDR3 of SEQ ID NO: 145; the CDR1, CDR2, and CDR3 of SEQ ID NO: 149;the CDR1, CDR2, and CDR3 of SEQ ID NO: 153; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 157; the CDR1, CDR2, and CDR3 of SEQ ID NO: 161; the CDR1,CDR2, and CDR3 of SEQ ID NO: 165; the CDR1, CDR2, and CDR3 of SEQ ID NO:169, the CDR1, CDR2, and CDR3 of SEQ ID NO: 173, the CDR1, CDR2, andCDR3 of SEQ ID NO: 177, the CDR1, CDR2, and CDR3 of SEQ ID NO: 181, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 185.

In some embodiments, the variable domain of the second light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 54; the CDR1, CDR2, andCDR3 of SEQ ID NO: 58; the CDR1, CDR2, and CDR3 of SEQ ID NO: 70; theCDR1, CDR2, and CDR3 of SEQ ID NO: 74; the CDR1, CDR2, and CDR3 of SEQID NO: 78; the CDR1, CDR2, and CDR3 of SEQ ID NO: 82; the CDR1, CDR2,and CDR3 of SEQ ID NO: 86; the CDR1, CDR2, and CDR3 of SEQ ID NO: 90;the CDR1, CDR2, and CDR3 of SEQ ID NO: 94; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 98; the CDR1, CDR2, and CDR3 of SEQ ID NO: 102; the CDR1,CDR2, and CDR3 of SEQ ID NO: 106; the CDR1, CDR2, and CDR3 of SEQ ID NO:110; the CDR1, CDR2, and CDR3 of SEQ ID NO: 118; the CDR1, CDR2, andCDR3 of SEQ ID NO: 122; the CDR1, CDR2, and CDR3 of SEQ ID NO: 126; theCDR1, CDR2, and CDR3 of SEQ ID NO: 130; the CDR1, CDR2, and CDR3 of SEQID NO: 134; the CDR1, CDR2, and CDR3 of SEQ ID NO: 142; the CDR1, CDR2,and CDR3 of SEQ ID NO: 146; the CDR1, CDR2, and CDR3 of SEQ ID NO: 150;the CDR1, CDR2, and CDR3 of SEQ ID NO: 154; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 158; the CDR1, CDR2, and CDR3 of SEQ ID NO: 162, the CDR1,CDR2, and CDR3 of SEQ ID NO: 166; the CDR1, CDR2, and CDR3 of SEQ ID NO:170, the CDR1, CDR2, and CDR3 of SEQ ID NO: 174, the CDR1, CDR2, andCDR3 of SEQ ID NO: 178, the CDR1, CDR2, and CDR3 of SEQ ID NO: 182, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 186.

In some embodiments, the molecule comprises SEQ ID NO: 51, SEQ ID NO:52, SEQ ID NO: 53, and SEQ ID NO: 54. In some embodiments, the moleculecomprises SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO:58. In some embodiments, the molecule comprises SEQ ID NO: 67, SEQ IDNO: 68, SEQ ID NO: 69, and SEQ ID NO: In some embodiments, the moleculecomprises SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO:74. In some embodiments, the molecule comprises SEQ ID NO: SEQ ID NO:76, SEQ ID NO: 77, and SEQ ID NO: 78. In some embodiments, the moleculecomprises SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO:82. In some embodiments, the molecule comprises SEQ ID NO: 83, SEQ IDNO: 84, SEQ ID NO: 85, and SEQ ID NO: 86. In some embodiments, themolecule comprises SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, and SEQID NO: 90. In some embodiments, the molecule comprises SEQ ID NO: 91,SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94. In some embodiments,the molecule comprises SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, andSEQ ID NO: 98. In some embodiments, the molecule comprises SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. In someembodiments, the molecule comprises SEQ ID NO: 103, SEQ ID NO: 104, SEQID NO: 105, and SEQ ID NO: 106. In some embodiments, the moleculecomprises SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, and SEQ ID NO:110. In some embodiments, the molecule comprises SEQ ID NO: 115, SEQ IDNO: 116, SEQ ID NO: 117, and SEQ ID NO: 118.

In some embodiments, the molecule comprises SEQ ID NO: 119, SEQ ID NO:120, SEQ ID NO: 121, and SEQ ID NO: 122. In some embodiments, themolecule comprises SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, andSEQ ID NO: 126. In some embodiments, the molecule comprises SEQ ID NO:127, SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130. In someembodiments, the molecule comprises SEQ ID NO: 131, SEQ ID NO: 132, SEQID NO: 133, and SEQ ID NO: 133. In some embodiments, the moleculecomprises SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, and SEQ ID NO:142. In some embodiments, the molecule comprises SEQ ID NO: 143, SEQ IDNO: 144, SEQ ID NO: 145, and SEQ ID NO: 146. In some embodiments, themolecule comprises SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, andSEQ ID NO: 150. In some embodiments, the molecule comprises SEQ ID NO:151, SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154. In someembodiments, the molecule comprises SEQ ID NO: 155, SEQ ID NO: 156, SEQID NO: 157, and SEQ ID NO: 158. In some embodiments, the moleculecomprises SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO:162. In some embodiments, the molecule comprises SEQ ID NO: 163, SEQ IDNO: 164, SEQ ID NO: 165, and SEQ ID NO: 166. In some embodiments, themolecule comprises SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, andSEQ ID NO: 170. In some embodiments, the molecule comprises SEQ ID NO:171, SEQ ID NO: 172, SEQ ID NO: 173, and SEQ ID NO: 174. In someembodiments, the molecule comprises SEQ ID NO: 175, SEQ ID NO: 176, SEQID NO: 177, and SEQ ID NO: 178. In some embodiments, the moleculecomprises SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO:182. In some embodiments, the molecule comprises SEQ ID NO: 183, SEQ IDNO: 184, SEQ ID NO: 185, and SEQ ID NO: 186.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 41. In some embodiments, the heavy chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 35. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23. In some embodiments,the heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 27. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 6. In some embodiments, the light chain variabledomain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 42. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 36. In some embodiments, the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 2.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 14. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 28. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 5 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 6. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 41 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 42. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 35 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 36.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 1 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 2.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 23 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 5 and the light chain variable domain comprises SEQ ID NO: 6. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO:41 and the light chain variable domain comprises SEQ ID NO: 42. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 35 andthe light chain variable domain comprises SEQ ID NO: 36. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 1 andthe light chain variable domain comprises SEQ ID NO: 2. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 23 andthe light chain variable domain comprises SEQ ID NO: 24. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 13 andthe light chain variable domain comprises SEQ ID NO: 14. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 27 andthe light chain variable domain comprises SEQ ID NO: 28. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 5. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:41. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 23. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 13. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 27.

In some embodiments, the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 6. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 42. In some embodiments, the light chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 36. In someembodiments, the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 2. In some embodiments, the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:24. In some embodiments, the light chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 14. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 28. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 5 and the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 6. In some embodiments, the heavy chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 41 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:42. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 35 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:36. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 23 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 24. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 13 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 14. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 27 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 28.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a N-Terminaldomain (NTD) of a spike protein. In some embodiments, the coronavirus isa SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a synthesized monoclonal antibody, or a functional fragmentthereof, comprising a heavy chain having a variable domain and aconstant domain and a light chain having a variable domain and aconstant domain, wherein the antibody binds an antigen on a coronavirusparticle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 41. In some embodiments, the heavy chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 35. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23. In some embodiments,the heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13. In someembodiments, the heavy chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27.In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 6.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 42. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 36. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 2. In some embodiments, the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 24. In some embodiments, thelight chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14. In some embodiments,the light chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 6.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 41 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 42. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 36. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 1 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 2. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 23 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 13 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 5 and the light chain variable domain comprises SEQ ID NO: 6. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO:41 and the light chain variable domain comprises SEQ ID NO: 42. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 35 andthe light chain variable domain comprises SEQ ID NO: 36. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 1 andthe light chain variable domain comprises SEQ ID NO: 2. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 23 andthe light chain variable domain comprises SEQ ID NO: 24. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 13 andthe light chain variable domain comprises SEQ ID NO: 14.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 27 and the light chain variable domain comprises SEQ ID NO: 28. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 5. In some embodiments, the heavychain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 41. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 1. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 23. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:13. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 27. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 6. In some embodiments, the light chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 42. In someembodiments, the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 36. In some embodiments, the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2. In some embodiments, the light chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 24.

In some embodiments, the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 14. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 28. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 5 and the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 6. In some embodiments, the heavy chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 41 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:42. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 35 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:36. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 23 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:24. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 13 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:14. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 27 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:28.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a N-Terminaldomain (NTD) of a spike protein. In some embodiments, the coronavirus isa SARS-CoV-2 coronavirus. In some embodiments, the antibody isadministered in combination with a second pharmaceutical agent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain. In some embodiments, the firstpolypeptide chain and the second polypeptide chain are covalently bondedto one another.

In some embodiments, the first heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 47,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 111, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 135, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 187, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 211.In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 48,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 112, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 136, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 188, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 212.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 49,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 113, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 137, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 189, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 213.In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 50,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 114, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 138, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 190, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 214.In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 13.

In some embodiments, the variable domain of the first light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 36, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14. In some embodiments, thevariable domain of the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 43. In some embodiments, the variable domainof the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 46,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 47; CDR1, CDR2, and CDR3 ofSEQ ID NO: 111; CDR1, CDR2, and CDR3 of SEQ ID NO: 135; CDR1, CDR2, andCDR3 of SEQ ID NO: 187; or CDR1, CDR2, and CDR3 of SEQ ID NO: 211. Insome embodiments, the variable domain of the first light chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 48, CDR1, CDR2, and CDR3 of SEQ IDNO: 112; CDR1, CDR2, and CDR3 of SEQ ID NO: 136; CDR1, CDR2, and CDR3 ofSEQ ID NO: 188; or CDR1, CDR2, and CDR3 of SEQ ID NO: 212. In someembodiments, the variable domain of the second heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 49, CDR1, CDR2, and CDR3 of SEQ IDNO: 113; CDR1, CDR2, and CDR3 of SEQ ID NO: 137; CDR1, CDR2, and CDR3 ofSEQ ID NO: 189; or CDR1, CDR2, and CDR3 of SEQ ID NO: 213. In someembodiments, the variable domain of the second light chain comprisesCDR1, CDR2, and CDR3 SEQ ID NO: 50, CDR1, CDR2, and CDR3 of SEQ ID NO:114; CDR1, CDR2, and CDR3 of SEQ ID NO: 138; CDR1, CDR2, and CDR3 of SEQID NO: 190; or CDR1, CDR2, and CDR3 of SEQ ID NO: 214.

In some embodiments, the molecule comprises SEQ ID NO: 47, SEQ ID NO:48, SEQ ID NO: 49, and SEQ ID NO: 50. In some embodiments, the moleculecomprises SEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO:114. In some embodiments, the molecule comprises SEQ ID NO: 135, SEQ IDNO: 135, SEQ ID NO: 137, and SEQ ID NO: 138. In some embodiments, themolecule comprises SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, andSEQ ID NO: 190. In some embodiments, the molecule comprises SEQ ID NO:211, SEQ ID NO: 212, SEQ ID NO: 213, and SEQ ID NO: 214.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a composition comprising abispecific molecule comprising a first polypeptide chain and a secondpolypeptide chain, wherein: the first polypeptide chain comprises: afirst light chain comprising a variable domain and a constant domain; afirst heavy chain comprising a variable domain and a constant domain;the second polypeptide chain comprises: a second light chain comprisinga variable domain and a constant domain; and a second heavy chaincomprising a variable domain and a constant domain. In some embodiments,the first polypeptide chain and the second polypeptide chain arecovalently bonded to one another.

In some embodiments, the first heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 47,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 111, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 135, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 187, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 211.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 48,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 112, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 136, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 188, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 212.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 49,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 113, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 137, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 189, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 213.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 50,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 114, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 138, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 190, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 214.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 13. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the variable domain of the secondheavy chain comprises a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 13, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 45, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43.

In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 14, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 46, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 47; CDR1, CDR2, and CDR3 ofSEQ ID NO: 111; CDR1, CDR2, and CDR3 of SEQ ID NO: 135; CDR1, CDR2, andCDR3 of SEQ ID NO: 187; or CDR1, CDR2, and CDR3 of SEQ ID NO: 211. Insome embodiments, the variable domain of the first light chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 48, CDR1, CDR2, and CDR3 of SEQ IDNO: 112; CDR1, CDR2, and CDR3 of SEQ ID NO: 136; CDR1, CDR2, and CDR3 ofSEQ ID NO: 188; or CDR1, CDR2, and CDR3 of SEQ ID NO: 212. In someembodiments, the variable domain of the second heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 49, CDR1, CDR2, and CDR3 of SEQ IDNO: 113; CDR1, CDR2, and CDR3 of SEQ ID NO: 137; CDR1, CDR2, and CDR3 ofSEQ ID NO: 189; or CDR1, CDR2, and CDR3 of SEQ ID NO: 213. In someembodiments, the variable domain of the second light chain comprisesCDR1, CDR2, and CDR3 SEQ ID NO: 50, CDR1, CDR2, and CDR3 of SEQ ID NO:114; CDR1, CDR2, and CDR3 of SEQ ID NO: 138; CDR1, CDR2, and CDR3 of SEQID NO: 190; or CDR1, CDR2, and CDR3 of SEQ ID NO: 214. In someembodiments, the molecule comprises SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, and SEQ ID NO: 50. In some embodiments, the molecule comprisesSEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO: 114. Insome embodiments, the molecule comprises SEQ ID NO: 135, SEQ ID NO: 135,SEQ ID NO: 137, and SEQ ID NO: 138. In some embodiments, the moleculecomprises SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, and SEQ ID NO:190. In some embodiments, the molecule comprises SEQ ID NO: 211, SEQ IDNO: 212, SEQ ID NO: 213, and SEQ ID NO: 214.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427.

In some embodiments, the molecule specifically recognizes a firstepitope and a second epitope on a SARS-CoV-2 particle. In someembodiments, the first epitope comprises at least a portion of areceptor binding domain (RBD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the second epitope comprises at least aportion of a N-terminal domain (NTD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the composition is administered incombination with a second therapeutic agent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3of SEQ ID NO: 63. In some embodiments, the variable domain of the firstlight chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1,CDR2, and CDR3 of SEQ ID NO: 64. In some embodiments, the variabledomain of the second heavy chain comprises CDR1, CDR2, and CDR3 of SEQID NO: 61 or CDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments,the variable domain of the second light chain comprises CDR1, CDR2, andCDR3 SEQ ID NO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on an S protein of aSARS-CoV-2 particle.

In certain aspects, the invention provides a method of treating aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a composition comprising a bispecificmolecule, wherein the bispecific molecule comprises a first polypeptidechain and a second polypeptide chain, wherein: the first polypeptidechain comprises: a first light chain comprising a variable domain and aconstant domain; a first heavy chain comprising a variable domain and aconstant domain; the second polypeptide chain comprises: a second lightchain comprising a variable domain and a constant domain; and a secondheavy chain comprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66. In someembodiments, the variable domain of the first heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3 of SEQ IDNO: 63. In some embodiments, the variable domain of the first lightchain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1, CDR2, andCDR3 of SEQ ID NO: 64. In some embodiments, the variable domain of thesecond heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 61 orCDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments, the variabledomain of the second light chain comprises CDR1, CDR2, and CDR3 SEQ IDNO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a method of preventing aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a composition comprising a bispecificmolecule, wherein the bispecific molecule comprises a first polypeptidechain and a second polypeptide chain, wherein: the first polypeptidechain comprises: a first light chain comprising a variable domain and aconstant domain; a first heavy chain comprising a variable domain and aconstant domain; the second polypeptide chain comprises: a second lightchain comprising a variable domain and a constant domain; and a secondheavy chain comprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 59 or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 63. In some embodiments, the first light chain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 60 or a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 64. In some embodiments, the second heavychain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 61 or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65. In some embodiments,the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 62 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 66.

In some embodiments, the first heavy chain comprises SEQ ID NO: 59 orSEQ ID NO: 63. In some embodiments, the first light chain comprises SEQID NO: 60 or SEQ ID NO: 64. In some embodiments, the second heavy chaincomprises SEQ ID NO: 61 or SEQ ID NO: 65. In some embodiments, thesecond light chain comprises SEQ ID NO: 62 or SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 59 or CDR1, CDR2, and CDR3of SEQ ID NO: 63. In some embodiments, the variable domain of the firstlight chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60 or CDR1,CDR2, and CDR3 of SEQ ID NO: 64. In some embodiments, the variabledomain of the second heavy chain comprises CDR1, CDR2, and CDR3 of SEQID NO: 61 or CDR1, CDR2, and CDR3 of SEQ ID NO: 65. In some embodiments,the variable domain of the second light chain comprises CDR1, CDR2, andCDR3 SEQ ID NO: 62 or CDR1, CDR2, and CDR3 of SEQ ID NO: 66.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28. In some embodiments, the variable domain ofthe second heavy chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27 or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 28 or a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14.

In some embodiments, the variable domain of the first heavy chaincomprises SEQ ID NO: 13 or SEQ ID NO: 27. In some embodiments, thevariable domain of the first light chain comprises SEQ ID NO: 14 or SEQID NO: 28. In some embodiments, the variable domain of the second heavychain comprises SEQ ID NO: 27 or SEQ ID NO: 13. In some embodiments, thevariable domain of the second light chain comprises SEQ ID NO: 28 or SEQID NO: 14.

In some embodiments, the molecule comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 59, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 60,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 61, and a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 62. In some embodiments, the moleculecomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NOs: 63, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 64, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 65, and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 66. In some embodiments, the molecule comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NOs: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, and a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the molecule comprises SEQ ID NOs: 59, 60, 61, and62. In some embodiments, the molecule comprises SEQ ID NOs: 63, 64, 65,and 66. In some embodiments, the molecule comprises SEQ ID NOs: 13, 14,27, and 28.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus strain. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on an S protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16. In some embodiments, theantibody comprises a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 15 and a polypeptide sequence which isat least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 16. In someembodiments, the antibody comprises SEQ ID NO: 15 and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of asynthesized monoclonal antibody, or a functional fragment thereof,comprising a heavy chain having a variable domain and a constant domainand a light chain having a variable domain and a constant domain,wherein the antibody binds an antigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody neutralizes a coronavirus. In some embodiments, the coronavirusis SARS-CoV-2. In some embodiments, the antibody specifically binds anepitope on the surface of the coronavirus. In some embodiments, theepitope comprises at least a portion of a coronavirus spike protein. Insome embodiments, the at least a portion of a coronavirus spike proteincomprises a receptor binding domain (RBD) of a spike protein. In someembodiments, the coronavirus is a SARS-CoV-2 coronavirus. In someembodiments, the antibody is administered in combination with a secondpharmaceutical agent.

In certain aspects, the invention provides a method of preventing aCOVID-19 infection in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of asynthesized monoclonal antibody, or a functional fragment thereof,comprising a heavy chain having a variable domain and a constant domainand a light chain having a variable and a constant domain, wherein theantibody binds an antigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16. In some embodiments, the heavy chainvariable domain comprises SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises SEQ ID NO: 16.

In some embodiments, the antibody comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 15 and apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16. In some embodiments, the antibody comprises SEQ ID NO: 15and SEQ ID NO: 16.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 15. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 16.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is SARS-CoV-2. In some embodiments, theantibody neutralizes a coronavirus. In some embodiments, the coronavirusis SARS-CoV-2. In some embodiments, the antibody specifically binds anepitope on the surface of the coronavirus. In some embodiments, theepitope comprises at least a portion of a coronavirus spike protein. Insome embodiments, the at least a portion of a coronavirus spike proteincomprises a receptor binding domain (RBD) of a spike protein. In someembodiments, the coronavirus is a SARS-CoV-2 coronavirus. In someembodiments, the antibody is administered in combination with a secondpharmaceutical agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 7, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 9, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 11, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 33, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 39, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 4, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 8, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 10, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 12, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 26, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 30, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 40, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 4.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 7 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 8.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 9 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 10.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 11 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 12. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 17 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 19 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 21 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 25 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 29 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 30.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 33 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 37 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 38. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 39 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 40. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 43 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 45 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 3 and the light chain variable domain comprises SEQ ID NO: 4. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO: 7and the light chain variable domain comprises SEQ ID NO: 8. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 9 andthe light chain variable domain comprises SEQ ID NO: 10. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 11 andthe light chain variable domain comprises SEQ ID NO: 12. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 17 andthe light chain variable domain comprises SEQ ID NO: 18. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 19 andthe light chain variable domain comprises SEQ ID NO: 20. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 21 andthe light chain variable domain comprises SEQ ID NO: 22. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 25 andthe light chain variable domain comprises SEQ ID NO: 26. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 29 andthe light chain variable domain comprises SEQ ID NO: 30. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 31 andthe light chain variable domain comprises SEQ ID NO: 32. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 33 andthe light chain variable domain comprises SEQ ID NO: 34. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 37 andthe light chain variable domain comprises SEQ ID NO: 38. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 39 andthe light chain variable domain comprises SEQ ID NO: 40. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 43 andthe light chain variable domain comprises SEQ ID NO: 44. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 45 andthe light chain variable domain comprises SEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 3; the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 7; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 9; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 11; or the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 17. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:19; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 21; the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 25; the CDR1, CDR2, and CDR3 regions ofSEQ ID NO: 29; or the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 31. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 33; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 37; the CDR1, CDR2, and CDR3 regions of SEQ ID NO:39; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 43; or the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 45. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 4; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 8; the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 10; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 12; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 18. In some embodiments, the light chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 20; the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 22; the CDR1, CDR2, and CDR3 regions of SEQID NO: 26; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 30; or theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 32. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 34; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 38; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 40; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 44; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 46.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427.

In some embodiments, the antibody specifically binds an epitope on thesurface of the coronavirus. In some embodiments, the epitope comprisesat least a portion of a coronavirus spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises areceptor binding domain (RBD) of a spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises aN-Terminal domain (NTD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a synthesized monoclonal antibody, or a functional fragmentthereof, comprising a heavy chain having a variable domain and aconstant domain and a light chain having a variable domain and aconstant domain, wherein the antibody binds an antigen on a coronavirusparticle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 7, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 9, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 11, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 31.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 33, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 39, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43, or apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 4, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 8, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 10, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 12, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 26, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 30, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 40, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 3 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 4.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 7 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 8.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 9 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 10.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 11 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 12. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 17 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 19 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 20.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 21 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 25 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 29 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 30. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 31 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 32. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 33 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 34. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 37 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 38.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 39 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 40. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 43 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 45 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 3 and the light chain variable domain comprises SEQ ID NO: 4. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO: 7and the light chain variable domain comprises SEQ ID NO: 8. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 9 andthe light chain variable domain comprises SEQ ID NO: 10. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 11 andthe light chain variable domain comprises SEQ ID NO: 12. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 17 andthe light chain variable domain comprises SEQ ID NO: 18. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 19 andthe light chain variable domain comprises SEQ ID NO: 20. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 21 andthe light chain variable domain comprises SEQ ID NO: 22. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 25 andthe light chain variable domain comprises SEQ ID NO: 26. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 29 andthe light chain variable domain comprises SEQ ID NO: 30. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 31 andthe light chain variable domain comprises SEQ ID NO: 32. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 33 andthe light chain variable domain comprises SEQ ID NO: 34. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 37 andthe light chain variable domain comprises SEQ ID NO: 38. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 39 andthe light chain variable domain comprises SEQ ID NO: 40. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 43 andthe light chain variable domain comprises SEQ ID NO: 44. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 45 andthe light chain variable domain comprises SEQ ID NO: 46.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 3; the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 7; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 9; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 11; or the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 17. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:19; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 21; the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 25; the CDR1, CDR2, and CDR3 regions ofSEQ ID NO: 29; or the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 31. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 33; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 37; the CDR1, CDR2, and CDR3 regions of SEQ ID NO:39; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 43; or the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 45. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 4; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 8; the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 10; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 12; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 18. In some embodiments, the light chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 20; the CDR1, CDR2, andCDR3 regions of SEQ ID NO: 22; the CDR1, CDR2, and CDR3 regions of SEQID NO: 26; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 30; or theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 32. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 34; the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 38; theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 40; the CDR1, CDR2, and CDR3regions of SEQ ID NO: 44; or the CDR1, CDR2, and CDR3 regions of SEQ IDNO: 46.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427.

In some embodiments, the antibody specifically binds an epitope on thesurface of the coronavirus. In some embodiments, the epitope comprisesat least a portion of a coronavirus spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises areceptor binding domain (RBD) of a spike protein. In some embodiments,the at least a portion of a coronavirus spike protein comprises aN-Terminal domain (NTD) of a spike protein. In some embodiments, thecoronavirus is a SARS-CoV-2 coronavirus. In some embodiments, thecomposition is administered in combination with a second therapeuticagent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 51, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 55, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 67, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 71, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 75, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 79, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 83, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 87, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 91, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 95, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 99, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 103, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 107, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 115, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 119, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 123, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 127,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 131, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 139, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 143, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 147,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 151, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 155, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 159, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 163,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 167, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 171, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 175, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 179,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:183.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 52,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 56, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 68; a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 72, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 76, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 80, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 84, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 88, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 92, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 96, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 100, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 104, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 108,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 116, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 120, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 124, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 128,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 132, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 140, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 144, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 148,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 152, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 156, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 160, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 164,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 168, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 172, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 176, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 180,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:184.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 53,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 57, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 69, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 73, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 77, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 81, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 85, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 89, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 93, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 97, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 101, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 105, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 109,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 117, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 121, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 125, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 129,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 133, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 141, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 145, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 149,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 153, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 157, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 161, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 165,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 169, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 173, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 177, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 181,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 185.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 54,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 58, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 70, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 74, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 78, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 82, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 86, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 90, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 94, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 98, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 102, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 106, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 110,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 118, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 122, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 126, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 130,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 134, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 142, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 146, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 150,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 154, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 158, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 162, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 166,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 170, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 174, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 178, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 182,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 186.

In some embodiments, variable domain of the first heavy chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 15, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 27, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 35, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 25, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 17, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 37, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 19, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 41.

In some embodiments, variable domain of the first light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 16, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 28, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 36, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 26, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 18, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 38, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 20, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 6, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 22, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 42.

In some embodiments, variable domain of the second heavy chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 27, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 5, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 19, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 21, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 29, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 35, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 23, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 25, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 37, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 39, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 43, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 9.

In some embodiments, variable domain of the second light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 6, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 30, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 26, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 40, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 10.

In some embodiments, the variable domain of the first heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 51; the CDR1, CDR2, andCDR3 of SEQ ID NO: the CDR1, CDR2, and CDR3 of SEQ ID NO: 67; the CDR1,CDR2, and CDR3 of SEQ ID NO: 71; the CDR1, CDR2, and CDR3 of SEQ ID NO:75; the CDR1, CDR2, and CDR3 of SEQ ID NO: 79; the CDR1, CDR2, and CDR3of SEQ ID NO: 83; the CDR1, CDR2, and CDR3 of SEQ ID NO: 87; the CDR1,CDR2, and CDR3 of SEQ ID NO: 91; the CDR1, CDR2, and CDR3 of SEQ ID NO:95; the CDR1, CDR2, and CDR3 of SEQ ID NO: 99; the CDR1, CDR2, and CDR3of SEQ ID NO: 103; the CDR1, CDR2, and CDR3 of SEQ ID NO: 107; the CDR1,CDR2, and CDR3 of SEQ ID NO: 115; the CDR1, CDR2, and CDR3 of SEQ ID NO:119, the CDR1, CDR2, and CDR3 of SEQ ID NO: 123, the CDR1, CDR2, andCDR3 of SEQ ID NO: 127; the CDR1, CDR2, and CDR3 of SEQ ID NO: 131; theCDR1, CDR2, and CDR3 of SEQ ID NO: 139; the CDR1, CDR2, and CDR3 of SEQID NO: 143; the CDR1, CDR2, and CDR3 of SEQ ID NO: 147; the CDR1, CDR2,and CDR3 of SEQ ID NO: 151; the CDR1, CDR2, and CDR3 of SEQ ID NO: 155;the CDR1, CDR2, and CDR3 of SEQ ID NO: 159; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 163; the CDR1, CDR2, and CDR3 of SEQ ID NO: 167, the CDR1,CDR2, and CDR3 of SEQ ID NO: 171, the CDR1, CDR2, and CDR3 of SEQ ID NO:175, the CDR1, CDR2, and CDR3 of SEQ ID NO: 179, or the CDR1, CDR2, andCDR3 of SEQ ID NO: 183.

In some embodiments, the variable domain of the first light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 52; the CDR1, CDR2, andCDR3 of SEQ ID NO: 56; the CDR1, CDR2, and CDR3 of SEQ ID NO: 68; theCDR1, CDR2, and CDR3 of SEQ ID NO: 72; the CDR1, CDR2, and CDR3 of SEQID NO: 76; the CDR1, CDR2, and CDR3 of SEQ ID NO: 80; the CDR1, CDR2,and CDR3 of SEQ ID NO: 84; the CDR1, CDR2, and CDR3 of SEQ ID NO: 88;the CDR1, CDR2, and CDR3 of SEQ ID NO: 92; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 96; the CDR1, CDR2, and CDR3 of SEQ ID NO: 100; the CDR1,CDR2, and CDR3 of SEQ ID NO: 104; the CDR1, CDR2, and CDR3 of SEQ ID NO:108; the CDR1, CDR2, and CDR3 of SEQ ID NO: 116; the CDR1, CDR2, andCDR3 of SEQ ID NO: 120; the CDR1, CDR2, and CDR3 of SEQ ID NO: 124; theCDR1, CDR2, and CDR3 of SEQ ID NO: 128; the CDR1, CDR2, and CDR3 of SEQID NO: 132; the CDR1, CDR2, and CDR3 of SEQ ID NO: 140; the CDR1, CDR2,and CDR3 of SEQ ID NO: 144; the CDR1, CDR2, and CDR3 of SEQ ID NO: 148;the CDR1, CDR2, and CDR3 of SEQ ID NO: 152; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 156; the CDR1, CDR2, and CDR3 of SEQ ID NO: 160; the CDR1,CDR2, and CDR3 of SEQ ID NO: 164; the CDR1, CDR2, and CDR3 of SEQ ID NO:168, the CDR1, CDR2, and CDR3 of SEQ ID NO: 172, the CDR1, CDR2, andCDR3 of SEQ ID NO: 176, the CDR1, CDR2, and CDR3 of SEQ ID NO: 180, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 184.

In some embodiments, the variable domain of the second heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 53; the CDR1, CDR2, andCDR3 of SEQ ID NO: 57; the CDR1, CDR2, and CDR3 of SEQ ID NO: 69; theCDR1, CDR2, and CDR3 of SEQ ID NO: 73; the CDR1, CDR2, and CDR3 of SEQID NO: 77; the CDR1, CDR2, and CDR3 of SEQ ID NO: 81; the CDR1, CDR2,and CDR3 of SEQ ID NO: 85; the CDR1, CDR2, and CDR3 of SEQ ID NO: 89;the CDR1, CDR2, and CDR3 of SEQ ID NO: 93; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 97; the CDR1, CDR2, and CDR3 of SEQ ID NO: 101; the CDR1,CDR2, and CDR3 of SEQ ID NO: 105; the CDR1, CDR2, and CDR3 of SEQ ID NO:109; the CDR1, CDR2, and CDR3 of SEQ ID NO: 117; the CDR1, CDR2, andCDR3 of SEQ ID NO: 121; the CDR1, CDR2, and CDR3 of SEQ ID NO: 125; theCDR1, CDR2, and CDR3 of SEQ ID NO: 129; the CDR1, CDR2, and CDR3 of SEQID NO: 133; the CDR1, CDR2, and CDR3 of SEQ ID NO: 141; the CDR1, CDR2,and CDR3 of SEQ ID NO: 145; the CDR1, CDR2, and CDR3 of SEQ ID NO: 149;the CDR1, CDR2, and CDR3 of SEQ ID NO: 153; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 157; the CDR1, CDR2, and CDR3 of SEQ ID NO: 161; the CDR1,CDR2, and CDR3 of SEQ ID NO: 165; the CDR1, CDR2, and CDR3 of SEQ ID NO:169, the CDR1, CDR2, and CDR3 of SEQ ID NO: 173, the CDR1, CDR2, andCDR3 of SEQ ID NO: 177, the CDR1, CDR2, and CDR3 of SEQ ID NO: 181, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 185.

In some embodiments, the variable domain of the second light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 54; the CDR1, CDR2, andCDR3 of SEQ ID NO: 58; the CDR1, CDR2, and CDR3 of SEQ ID NO: 70; theCDR1, CDR2, and CDR3 of SEQ ID NO: 74; the CDR1, CDR2, and CDR3 of SEQID NO: 78; the CDR1, CDR2, and CDR3 of SEQ ID NO: 82; the CDR1, CDR2,and CDR3 of SEQ ID NO: 86; the CDR1, CDR2, and CDR3 of SEQ ID NO: 90;the CDR1, CDR2, and CDR3 of SEQ ID NO: 94; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 98; the CDR1, CDR2, and CDR3 of SEQ ID NO: 102; the CDR1,CDR2, and CDR3 of SEQ ID NO: 106; the CDR1, CDR2, and CDR3 of SEQ ID NO:110; the CDR1, CDR2, and CDR3 of SEQ ID NO: 118; the CDR1, CDR2, andCDR3 of SEQ ID NO: 122; the CDR1, CDR2, and CDR3 of SEQ ID NO: 126; theCDR1, CDR2, and CDR3 of SEQ ID NO: 130; the CDR1, CDR2, and CDR3 of SEQID NO: 134; the CDR1, CDR2, and CDR3 of SEQ ID NO: 142; the CDR1, CDR2,and CDR3 of SEQ ID NO: 146; the CDR1, CDR2, and CDR3 of SEQ ID NO: 150;the CDR1, CDR2, and CDR3 of SEQ ID NO: 154; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 158; the CDR1, CDR2, and CDR3 of SEQ ID NO: 162, the CDR1,CDR2, and CDR3 of SEQ ID NO: 166; the CDR1, CDR2, and CDR3 of SEQ ID NO:170, the CDR1, CDR2, and CDR3 of SEQ ID NO: 174, the CDR1, CDR2, andCDR3 of SEQ ID NO: 178, the CDR1, CDR2, and CDR3 of SEQ ID NO: 182, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 186.

In some embodiments, the molecule comprises SEQ ID NO: 51, SEQ ID NO:52, SEQ ID NO: 53, and SEQ ID NO: 54. In some embodiments, the moleculecomprises SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO:58. In some embodiments, the molecule comprises SEQ ID NO: 67, SEQ IDNO: 68, SEQ ID NO: 69, and SEQ ID NO: In some embodiments, the moleculecomprises SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO:74. In some embodiments, the molecule comprises SEQ ID NO: SEQ ID NO:76, SEQ ID NO: 77, and SEQ ID NO: 78. In some embodiments, the moleculecomprises SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO:82. In some embodiments, the molecule comprises SEQ ID NO: 83, SEQ IDNO: 84, SEQ ID NO: 85, and SEQ ID NO: 86. In some embodiments, themolecule comprises SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, and SEQID NO: 90. In some embodiments, the molecule comprises SEQ ID NO: 91,SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94. In some embodiments,the molecule comprises SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, andSEQ ID NO: 98. In some embodiments, the molecule comprises SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. In someembodiments, the molecule comprises SEQ ID NO: 103, SEQ ID NO: 104, SEQID NO: 105, and SEQ ID NO: 106. In some embodiments, the moleculecomprises SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, and SEQ ID NO:110. In some embodiments, the molecule comprises SEQ ID NO: 115, SEQ IDNO: 116, SEQ ID NO: 117, and SEQ ID NO: 118. In some embodiments, themolecule comprises SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, andSEQ ID NO: 122.

In some embodiments, the molecule comprises SEQ ID NO: 123, SEQ ID NO:124, SEQ ID NO: 125, and SEQ ID NO: 126. In some embodiments, themolecule comprises SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, andSEQ ID NO: 130. In some embodiments, the molecule comprises SEQ ID NO:131, SEQ ID NO: 132, SEQ ID NO: 133, and SEQ ID NO: 133. In someembodiments, the molecule comprises SEQ ID NO: 139, SEQ ID NO: 140, SEQID NO: 141, and SEQ ID NO: 142. In some embodiments, the moleculecomprises SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, and SEQ ID NO:146. In some embodiments, the molecule comprises SEQ ID NO: 147, SEQ IDNO: 148, SEQ ID NO: 149, and SEQ ID NO: 150. In some embodiments, themolecule comprises SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, andSEQ ID NO: 154. In some embodiments, the molecule comprises SEQ ID NO:155, SEQ ID NO: 156, SEQ ID NO: 157, and SEQ ID NO: 158. In someembodiments, the molecule comprises SEQ ID NO: 159, SEQ ID NO: 160, SEQID NO: 161, and SEQ ID NO: 162. In some embodiments, the moleculecomprises SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, and SEQ ID NO:166. In some embodiments, the molecule comprises SEQ ID NO: 167, SEQ IDNO: 168, SEQ ID NO: 169, and SEQ ID NO: 170. In some embodiments, themolecule comprises SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, andSEQ ID NO: 174. In some embodiments, the molecule comprises SEQ ID NO:175, SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178. In someembodiments, the molecule comprises SEQ ID NO: 179, SEQ ID NO: 180, SEQID NO: 181, and SEQ ID NO: 182. In some embodiments, the moleculecomprises SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, and SEQ ID NO:186.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427.

In some embodiments, the molecule specifically recognizes a firstepitope and a second epitope on a SARS-CoV-2 particle. In someembodiments, the first epitope comprises at least a portion of areceptor binding domain (RBD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the second epitope comprises at least aportion of a N-terminal domain (NTD) on a spike protein of a SARS-CoV-2particle.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a composition comprising abispecific molecule comprising a first polypeptide chain and a secondpolypeptide chain, wherein: the first polypeptide chain comprises: afirst light chain comprising a variable domain and a constant domain; afirst heavy chain comprising a variable domain and a constant domain;the second polypeptide chain comprises: a second light chain comprisinga variable domain and a constant domain; and a second heavy chaincomprising a variable domain and a constant domain.

In some embodiments, the first polypeptide chain and the secondpolypeptide chain are covalently bonded to one another. In someembodiments, the first heavy chain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 51, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 55, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 67, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 71, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 75, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 79, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 83, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 87, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 91, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 95, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 99, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 103, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 107, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 115, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 119, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 123, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 127,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 131, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 139, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 143, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 147,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 151, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 155, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 159, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 163,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 167, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 171, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 175, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 179,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:183.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 52,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 56, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 68; a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 72, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 76, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 80, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 84, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 88, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 92, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 96, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 100, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 104, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 108,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 116, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 120, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 124, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 128,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 132, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 140, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 144, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 148,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 152, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 156, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 160, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 164,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 168, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 172, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 176, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 180,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO:184.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 53,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 57, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 69, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 73, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 77, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 81, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 85, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 89, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 93, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 97, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 101, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 105, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 109,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 117, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 121, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 125, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 129,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 133, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 141, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 145, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 149,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 153, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 157, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 161, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 165,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 169, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 173, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 177, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 181,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 185.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 54,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 58, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 70, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 74, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 78, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 82, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 86, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 90, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 94, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 98, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 102, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 106, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 110,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 118, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 122, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 126, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 130,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 134, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 142, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 146, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 150,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 154, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 158, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 162, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 166,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 170, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 174, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 178, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 182,or a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%,72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 186.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 15, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 27, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 35, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 25, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 17, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 37, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 19, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 13, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 5, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 21, or a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 41.

In some embodiments, the variable domain of the first light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 28, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 26, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 18, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 6, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 22, or a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 42.

In some embodiments, the variable domain of the second heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 15, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 5, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 19, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 21, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 15, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 29, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 35, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 23, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 25, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 37, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 39, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 43, or a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 9.

In some embodiments, variable domain of the second light chain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 6, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 20, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 22, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 16, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 30, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 26, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 38, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 40, apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44, or a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 10.

In some embodiments, the variable domain of the first heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 51; the CDR1, CDR2, andCDR3 of SEQ ID NO: the CDR1, CDR2, and CDR3 of SEQ ID NO: 67; the CDR1,CDR2, and CDR3 of SEQ ID NO: 71; the CDR1, CDR2, and CDR3 of SEQ ID NO:75; the CDR1, CDR2, and CDR3 of SEQ ID NO: 79; the CDR1, CDR2, and CDR3of SEQ ID NO: 83; the CDR1, CDR2, and CDR3 of SEQ ID NO: 87; the CDR1,CDR2, and CDR3 of SEQ ID NO: 91; the CDR1, CDR2, and CDR3 of SEQ ID NO:95; the CDR1, CDR2, and CDR3 of SEQ ID NO: 99; the CDR1, CDR2, and CDR3of SEQ ID NO: 103; the CDR1, CDR2, and CDR3 of SEQ ID NO: 107; the CDR1,CDR2, and CDR3 of SEQ ID NO: 115; the CDR1, CDR2, and CDR3 of SEQ ID NO:119, the CDR1, CDR2, and CDR3 of SEQ ID NO: 123, the CDR1, CDR2, andCDR3 of SEQ ID NO: 127; the CDR1, CDR2, and CDR3 of SEQ ID NO: 131; theCDR1, CDR2, and CDR3 of SEQ ID NO: 139; the CDR1, CDR2, and CDR3 of SEQID NO: 143; the CDR1, CDR2, and CDR3 of SEQ ID NO: 147; the CDR1, CDR2,and CDR3 of SEQ ID NO: 151; the CDR1, CDR2, and CDR3 of SEQ ID NO: 155;the CDR1, CDR2, and CDR3 of SEQ ID NO: 159; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 163; the CDR1, CDR2, and CDR3 of SEQ ID NO: 167, the CDR1,CDR2, and CDR3 of SEQ ID NO: 171, the CDR1, CDR2, and CDR3 of SEQ ID NO:175, the CDR1, CDR2, and CDR3 of SEQ ID NO: 179, or the CDR1, CDR2, andCDR3 of SEQ ID NO: 183.

In some embodiments, the variable domain of the first light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 52; the CDR1, CDR2, andCDR3 of SEQ ID NO: 56; the CDR1, CDR2, and CDR3 of SEQ ID NO: 68; theCDR1, CDR2, and CDR3 of SEQ ID NO: 72; the CDR1, CDR2, and CDR3 of SEQID NO: 76; the CDR1, CDR2, and CDR3 of SEQ ID NO: 80; the CDR1, CDR2,and CDR3 of SEQ ID NO: 84; the CDR1, CDR2, and CDR3 of SEQ ID NO: 88;the CDR1, CDR2, and CDR3 of SEQ ID NO: 92; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 96; the CDR1, CDR2, and CDR3 of SEQ ID NO: 100; the CDR1,CDR2, and CDR3 of SEQ ID NO: 104; the CDR1, CDR2, and CDR3 of SEQ ID NO:108; the CDR1, CDR2, and CDR3 of SEQ ID NO: 116; the CDR1, CDR2, andCDR3 of SEQ ID NO: 120; the CDR1, CDR2, and CDR3 of SEQ ID NO: 124; theCDR1, CDR2, and CDR3 of SEQ ID NO: 128; the CDR1, CDR2, and CDR3 of SEQID NO: 132; the CDR1, CDR2, and CDR3 of SEQ ID NO: 140; the CDR1, CDR2,and CDR3 of SEQ ID NO: 144; the CDR1, CDR2, and CDR3 of SEQ ID NO: 148;the CDR1, CDR2, and CDR3 of SEQ ID NO: 152; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 156; the CDR1, CDR2, and CDR3 of SEQ ID NO: 160; the CDR1,CDR2, and CDR3 of SEQ ID NO: 164; the CDR1, CDR2, and CDR3 of SEQ ID NO:168, the CDR1, CDR2, and CDR3 of SEQ ID NO: 172, the CDR1, CDR2, andCDR3 of SEQ ID NO: 176, the CDR1, CDR2, and CDR3 of SEQ ID NO: 180, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 184.

In some embodiments, the variable domain of the second heavy chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 53; the CDR1, CDR2, andCDR3 of SEQ ID NO: 57; the CDR1, CDR2, and CDR3 of SEQ ID NO: 69; theCDR1, CDR2, and CDR3 of SEQ ID NO: 73; the CDR1, CDR2, and CDR3 of SEQID NO: 77; the CDR1, CDR2, and CDR3 of SEQ ID NO: 81; the CDR1, CDR2,and CDR3 of SEQ ID NO: 85; the CDR1, CDR2, and CDR3 of SEQ ID NO: 89;the CDR1, CDR2, and CDR3 of SEQ ID NO: 93; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 97; the CDR1, CDR2, and CDR3 of SEQ ID NO: 101; the CDR1,CDR2, and CDR3 of SEQ ID NO: 105; the CDR1, CDR2, and CDR3 of SEQ ID NO:109; the CDR1, CDR2, and CDR3 of SEQ ID NO: 117; the CDR1, CDR2, andCDR3 of SEQ ID NO: 121; the CDR1, CDR2, and CDR3 of SEQ ID NO: 125; theCDR1, CDR2, and CDR3 of SEQ ID NO: 129; the CDR1, CDR2, and CDR3 of SEQID NO: 133; the CDR1, CDR2, and CDR3 of SEQ ID NO: 141; the CDR1, CDR2,and CDR3 of SEQ ID NO: 145; the CDR1, CDR2, and CDR3 of SEQ ID NO: 149;the CDR1, CDR2, and CDR3 of SEQ ID NO: 153; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 157; the CDR1, CDR2, and CDR3 of SEQ ID NO: 161; the CDR1,CDR2, and CDR3 of SEQ ID NO: 165; the CDR1, CDR2, and CDR3 of SEQ ID NO:169, the CDR1, CDR2, and CDR3 of SEQ ID NO: 173, the CDR1, CDR2, andCDR3 of SEQ ID NO: 177, the CDR1, CDR2, and CDR3 of SEQ ID NO: 181, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 185.

In some embodiments, the variable domain of the second light chaincomprises the CDR1, CDR2, and CDR3 of SEQ ID NO: 54; the CDR1, CDR2, andCDR3 of SEQ ID NO: 58; the CDR1, CDR2, and CDR3 of SEQ ID NO: 70; theCDR1, CDR2, and CDR3 of SEQ ID NO: 74; the CDR1, CDR2, and CDR3 of SEQID NO: 78; the CDR1, CDR2, and CDR3 of SEQ ID NO: 82; the CDR1, CDR2,and CDR3 of SEQ ID NO: 86; the CDR1, CDR2, and CDR3 of SEQ ID NO: 90;the CDR1, CDR2, and CDR3 of SEQ ID NO: 94; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 98; the CDR1, CDR2, and CDR3 of SEQ ID NO: 102; the CDR1,CDR2, and CDR3 of SEQ ID NO: 106; the CDR1, CDR2, and CDR3 of SEQ ID NO:110; the CDR1, CDR2, and CDR3 of SEQ ID NO: 118; the CDR1, CDR2, andCDR3 of SEQ ID NO: 122; the CDR1, CDR2, and CDR3 of SEQ ID NO: 126; theCDR1, CDR2, and CDR3 of SEQ ID NO: 130; the CDR1, CDR2, and CDR3 of SEQID NO: 134; the CDR1, CDR2, and CDR3 of SEQ ID NO: 142; the CDR1, CDR2,and CDR3 of SEQ ID NO: 146; the CDR1, CDR2, and CDR3 of SEQ ID NO: 150;the CDR1, CDR2, and CDR3 of SEQ ID NO: 154; the CDR1, CDR2, and CDR3 ofSEQ ID NO: 158; the CDR1, CDR2, and CDR3 of SEQ ID NO: 162, the CDR1,CDR2, and CDR3 of SEQ ID NO: 166; the CDR1, CDR2, and CDR3 of SEQ ID NO:170, the CDR1, CDR2, and CDR3 of SEQ ID NO: 174, the CDR1, CDR2, andCDR3 of SEQ ID NO: 178, the CDR1, CDR2, and CDR3 of SEQ ID NO: 182, orthe CDR1, CDR2, and CDR3 of SEQ ID NO: 186.

In some embodiments, the molecule comprises SEQ ID NO: 51, SEQ ID NO:52, SEQ ID NO: 53, and SEQ ID NO: 54. In some embodiments, the moleculecomprises SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, and SEQ ID NO:58. In some embodiments, the molecule comprises SEQ ID NO: 67, SEQ IDNO: 68, SEQ ID NO: 69, and SEQ ID NO: In some embodiments, the moleculecomprises SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, and SEQ ID NO:74. In some embodiments, the molecule comprises SEQ ID NO: SEQ ID NO:76, SEQ ID NO: 77, and SEQ ID NO: 78. In some embodiments, the moleculecomprises SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, and SEQ ID NO:82. In some embodiments, the molecule comprises SEQ ID NO: 83, SEQ IDNO: 84, SEQ ID NO: 85, and SEQ ID NO: 86. In some embodiments, themolecule comprises SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, and SEQID NO: 90. In some embodiments, the molecule comprises SEQ ID NO: 91,SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94. In some embodiments,the molecule comprises SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, andSEQ ID NO: 98. In some embodiments, the molecule comprises SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, and SEQ ID NO: 102. In someembodiments, the molecule comprises SEQ ID NO: 103, SEQ ID NO: 104, SEQID NO: 105, and SEQ ID NO: 106. In some embodiments, the moleculecomprises SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, and SEQ ID NO:110. In some embodiments, the molecule comprises SEQ ID NO: 115, SEQ IDNO: 116, SEQ ID NO: 117, and SEQ ID NO: 118.

In some embodiments, the molecule comprises SEQ ID NO: 119, SEQ ID NO:120, SEQ ID NO: 121, and SEQ ID NO: 122. In some embodiments, themolecule comprises SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, andSEQ ID NO: 126. In some embodiments, the molecule comprises SEQ ID NO:127, SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130. In someembodiments, the molecule comprises SEQ ID NO: 131, SEQ ID NO: 132, SEQID NO: 133, and SEQ ID NO: 133. In some embodiments, the moleculecomprises SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, and SEQ ID NO:142. In some embodiments, the molecule comprises SEQ ID NO: 143, SEQ IDNO: 144, SEQ ID NO: 145, and SEQ ID NO: 146. In some embodiments, themolecule comprises SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, andSEQ ID NO: 150. In some embodiments, the molecule comprises SEQ ID NO:151, SEQ ID NO: 152, SEQ ID NO: 153, and SEQ ID NO: 154. In someembodiments, the molecule comprises SEQ ID NO: 155, SEQ ID NO: 156, SEQID NO: 157, and SEQ ID NO: 158. In some embodiments, the moleculecomprises SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, and SEQ ID NO:162. In some embodiments, the molecule comprises SEQ ID NO: 163, SEQ IDNO: 164, SEQ ID NO: 165, and SEQ ID NO: 166. In some embodiments, themolecule comprises SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, andSEQ ID NO: 170. In some embodiments, the molecule comprises SEQ ID NO:171, SEQ ID NO: 172, SEQ ID NO: 173, and SEQ ID NO: 174. In someembodiments, the molecule comprises SEQ ID NO: 175, SEQ ID NO: 176, SEQID NO: 177, and SEQ ID NO: 178. In some embodiments, the moleculecomprises SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, and SEQ ID NO:182. In some embodiments, the molecule comprises SEQ ID NO: 183, SEQ IDNO: 184, SEQ ID NO: 185, and SEQ ID NO: 186.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the composition isadministered in combination with a second therapeutic agent.

In certain aspects, the invention provides a synthesized monoclonalantibody, or a functional fragment thereof, comprising a heavy chainhaving a variable domain and a constant domain and a light chain havinga variable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 41. In some embodiments, the heavy chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 35. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23. In some embodiments,the heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 27. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 6. In some embodiments, the light chain variabledomain comprises a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 42. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 36. In some embodiments, the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 2.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 14. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 28. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 5 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 6. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 41 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 42. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 35 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 36.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 1 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 2.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 23 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 13 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 5 and the light chain variable domain comprises SEQ ID NO: 6. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO:41 and the light chain variable domain comprises SEQ ID NO: 42. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 35 andthe light chain variable domain comprises SEQ ID NO: 36. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 1 andthe light chain variable domain comprises SEQ ID NO: 2. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 23 andthe light chain variable domain comprises SEQ ID NO: 24. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 13 andthe light chain variable domain comprises SEQ ID NO: 14. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 27 andthe light chain variable domain comprises SEQ ID NO: 28. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 5. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:41. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 23. In some embodiments, the heavychain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 13. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 27.

In some embodiments, the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 6. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 42. In some embodiments, the light chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 36. In someembodiments, the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 2. In some embodiments, the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:24. In some embodiments, the light chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 14. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 28. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 5 and the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 6. In some embodiments, the heavy chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 41 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:42. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 35 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:36. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2.

In some embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 23 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 24. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 13 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 14. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 27 and the light chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 28.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a N-Terminaldomain (NTD) of a spike protein. In some embodiments, the coronavirus isa SARS-CoV-2 coronavirus.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of a synthesized monoclonal antibody, or a functional fragmentthereof, comprising a heavy chain having a variable domain and aconstant domain and a light chain having a variable domain and aconstant domain, wherein the antibody binds an antigen on a coronavirusparticle.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 41. In some embodiments, the heavy chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 35. In some embodiments, the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1. In some embodiments, theheavy chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23. In some embodiments,the heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13. In someembodiments, the heavy chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 27.In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 6.

In some embodiments, the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 42. In some embodiments, the light chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 36. In some embodiments, the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO: 2. In some embodiments, the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 24. In some embodiments, thelight chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14. In some embodiments,the light chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 5 and the light chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 6.In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 41 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 42. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 36. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 1 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 2. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 23 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 24.

In some embodiments, the heavy chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 13 and the light chain variable domain comprises apolypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the heavy chain variable domaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 27 and the light chain variable domain comprisesa polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 28.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 5 and the light chain variable domain comprises SEQ ID NO: 6. Insome embodiments, the heavy chain variable domain comprises SEQ ID NO:41 and the light chain variable domain comprises SEQ ID NO: 42. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 35 andthe light chain variable domain comprises SEQ ID NO: 36. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 1 andthe light chain variable domain comprises SEQ ID NO: 2. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 23 andthe light chain variable domain comprises SEQ ID NO: 24. In someembodiments, the heavy chain variable domain comprises SEQ ID NO: 13 andthe light chain variable domain comprises SEQ ID NO: 14.

In some embodiments, the heavy chain variable domain comprises SEQ IDNO: 27 and the light chain variable domain comprises SEQ ID NO: 28. Insome embodiments, the heavy chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 5. In some embodiments, the heavychain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 41. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 1. In someembodiments, the heavy chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 23. In some embodiments, the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:13. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 27. In some embodiments, thelight chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 6. In some embodiments, the light chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 42. In someembodiments, the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO: 36. In some embodiments, the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2. In some embodiments, the light chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 24.

In some embodiments, the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO: 14. In some embodiments, the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 28. In some embodiments, the heavy chain variable domaincomprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 5 and the lightchain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 6. In some embodiments, the heavy chain variable domain comprisesthe CDR1, CDR2, and CDR3 regions of SEQ ID NO: 41 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:42. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 35 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:36. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:2. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 23 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:24. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 13 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:14. In some embodiments, the heavy chain variable domain comprises theCDR1, CDR2, and CDR3 regions of SEQ ID NO: 27 and the light chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:28.

In some embodiments, the antibody neutralizes a coronavirus. In someembodiments, the coronavirus is a SARS-CoV-2 virus. In some embodiments,the coronavirus is a SARS-CoV-2 variant strain. In some embodiments, thevariant strain is selected from the group consisting of WA1, B.1.1.7,B1.526, B1.351, P1, B1.352, and B.1.427. In some embodiments, theantibody specifically binds an epitope on the surface of thecoronavirus. In some embodiments, the epitope comprises at least aportion of a coronavirus spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a receptorbinding domain (RBD) of a spike protein. In some embodiments, the atleast a portion of a coronavirus spike protein comprises a N-Terminaldomain (NTD) of a spike protein. In some embodiments, the coronavirus isa SARS-CoV-2 coronavirus. In some embodiments, the antibody isadministered in combination with a second pharmaceutical agent.

In certain aspects, the invention provides a bispecific moleculecomprising a first polypeptide chain and a second polypeptide chain,wherein: the first polypeptide chain comprises: a first light chaincomprising a variable domain and a constant domain; a first heavy chaincomprising a variable domain and a constant domain; the secondpolypeptide chain comprises: a second light chain comprising a variabledomain and a constant domain; and a second heavy chain comprising avariable domain and a constant domain. In some embodiments, the firstpolypeptide chain and the second polypeptide chain are covalently bondedto one another.

In some embodiments, the first heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 47,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 111, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 135, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 187, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 211.In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 48,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 112, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 136, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 188, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 212.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 49,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 113, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 137, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 189, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 213.In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 50,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 114, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 138, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 190, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 214.In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 13.

In some embodiments, the variable domain of the first light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 36, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 14. In some embodiments, thevariable domain of the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 13,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 45, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 43. In some embodiments, the variable domainof the second light chain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 14, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 46,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 44.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 47; CDR1, CDR2, and CDR3 ofSEQ ID NO: 111; CDR1, CDR2, and CDR3 of SEQ ID NO: 135; CDR1, CDR2, andCDR3 of SEQ ID NO: 187; or CDR1, CDR2, and CDR3 of SEQ ID NO: 211. Insome embodiments, the variable domain of the first light chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 48, CDR1, CDR2, and CDR3 of SEQ IDNO: 112; CDR1, CDR2, and CDR3 of SEQ ID NO: 136; CDR1, CDR2, and CDR3 ofSEQ ID NO: 188; or CDR1, CDR2, and CDR3 of SEQ ID NO: 212. In someembodiments, the variable domain of the second heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 49, CDR1, CDR2, and CDR3 of SEQ IDNO: 113; CDR1, CDR2, and CDR3 of SEQ ID NO: 137; CDR1, CDR2, and CDR3 ofSEQ ID NO: 189; or CDR1, CDR2, and CDR3 of SEQ ID NO: 213. In someembodiments, the variable domain of the second light chain comprisesCDR1, CDR2, and CDR3 SEQ ID NO: 50, CDR1, CDR2, and CDR3 of SEQ ID NO:114; CDR1, CDR2, and CDR3 of SEQ ID NO: 138; CDR1, CDR2, and CDR3 of SEQID NO: 190; or CDR1, CDR2, and CDR3 of SEQ ID NO: 214.

In some embodiments, the molecule comprises SEQ ID NO: 47, SEQ ID NO:48, SEQ ID NO: 49, and SEQ ID NO: 50. In some embodiments, the moleculecomprises SEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO:114. In some embodiments, the molecule comprises SEQ ID NO: 135, SEQ IDNO: 135, SEQ ID NO: 137, and SEQ ID NO: 138. In some embodiments, themolecule comprises SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, andSEQ ID NO: 190. In some embodiments, the molecule comprises SEQ ID NO:211, SEQ ID NO: 212, SEQ ID NO: 213, and SEQ ID NO: 214.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427. In some embodiments, the molecule specificallyrecognizes a first epitope and a second epitope on a SARS-CoV-2particle. In some embodiments, the first epitope comprises at least aportion of a receptor binding domain (RBD) on a spike protein of aSARS-CoV-2 particle. In some embodiments, the second epitope comprisesat least a portion of a N-terminal domain (NTD) on a spike protein of aSARS-CoV-2 particle.

In certain aspects, the invention provides a method of treating orpreventing a COVID-19 infection in a subject in need thereof, the methodcomprising administering to the subject a composition comprising abispecific molecule comprising a first polypeptide chain and a secondpolypeptide chain, wherein: the first polypeptide chain comprises: afirst light chain comprising a variable domain and a constant domain; afirst heavy chain comprising a variable domain and a constant domain;the second polypeptide chain comprises: a second light chain comprisinga variable domain and a constant domain; and a second heavy chaincomprising a variable domain and a constant domain. In some embodiments,the first polypeptide chain and the second polypeptide chain arecovalently bonded to one another.

In some embodiments, the first heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 47,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 111, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 135, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 187, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 211.

In some embodiments, the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 48,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 112, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 136, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 188, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 212.

In some embodiments, the second heavy chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 49,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 113, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 137, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 189, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 213.

In some embodiments, the second light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 50,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 114, a polypeptide sequence which is at least 60%, 62%, 65%,67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%,99% identical to SEQ ID NO: 138, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 190, or a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 214.

In some embodiments, the variable domain of the first heavy chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 35, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 13. In some embodiments, thevariable domain of the first light chain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 36,a polypeptide sequence which is at least 60%, 62%, 65%, 67%, 70%, 72%,75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical toSEQ ID NO: 14. In some embodiments, the variable domain of the secondheavy chain comprises a polypeptide sequence which is at least 60%, 62%,65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%,98%, 99% identical to SEQ ID NO: 13, a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 45, a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 43.

In some embodiments, the variable domain of the second light chaincomprises a polypeptide sequence which is at least 60%, 62%, 65%, 67%,70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99%identical to SEQ ID NO: 14, a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 46, a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 44.

In some embodiments, the variable domain of the first heavy chaincomprises CDR1, CDR2, and CDR3 of SEQ ID NO: 47; CDR1, CDR2, and CDR3 ofSEQ ID NO: 111; CDR1, CDR2, and CDR3 of SEQ ID NO: 135; CDR1, CDR2, andCDR3 of SEQ ID NO: 187; or CDR1, CDR2, and CDR3 of SEQ ID NO: 211. Insome embodiments, the variable domain of the first light chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 48, CDR1, CDR2, and CDR3 of SEQ IDNO: 112; CDR1, CDR2, and CDR3 of SEQ ID NO: 136; CDR1, CDR2, and CDR3 ofSEQ ID NO: 188; or CDR1, CDR2, and CDR3 of SEQ ID NO: 212. In someembodiments, the variable domain of the second heavy chain comprisesCDR1, CDR2, and CDR3 of SEQ ID NO: 49, CDR1, CDR2, and CDR3 of SEQ IDNO: 113; CDR1, CDR2, and CDR3 of SEQ ID NO: 137; CDR1, CDR2, and CDR3 ofSEQ ID NO: 189; or CDR1, CDR2, and CDR3 of SEQ ID NO: 213. In someembodiments, the variable domain of the second light chain comprisesCDR1, CDR2, and CDR3 SEQ ID NO: 50, CDR1, CDR2, and CDR3 of SEQ ID NO:114; CDR1, CDR2, and CDR3 of SEQ ID NO: 138; CDR1, CDR2, and CDR3 of SEQID NO: 190; or CDR1, CDR2, and CDR3 of SEQ ID NO: 214. In someembodiments, the molecule comprises SEQ ID NO: 47, SEQ ID NO: 48, SEQ IDNO: 49, and SEQ ID NO: 50. In some embodiments, the molecule comprisesSEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, and SEQ ID NO: 114. Insome embodiments, the molecule comprises SEQ ID NO: 135, SEQ ID NO: 135,SEQ ID NO: 137, and SEQ ID NO: 138. In some embodiments, the moleculecomprises SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, and SEQ ID NO:190. In some embodiments, the molecule comprises SEQ ID NO: 211, SEQ IDNO: 212, SEQ ID NO: 213, and SEQ ID NO: 214.

In some embodiments, the molecule further comprises one or moredisulfide bonds. In some embodiments, the molecule further comprises oneor more linker sequences. In some embodiments, the molecule is capableof neutralizing a coronavirus. In some embodiments, the coronavirus is aSARS-CoV-2 virus. In some embodiments, the SARS-CoV-2 virus strain isselected from the group consisting of WA1, B.1.1.7, B1.526, B1.351, P1,B1.352, and B.1.427.

In some embodiments, the molecule specifically recognizes a firstepitope and a second epitope on a SARS-CoV-2 particle. In someembodiments, the first epitope comprises at least a portion of areceptor binding domain (RBD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the second epitope comprises at least aportion of a N-terminal domain (NTD) on a spike protein of a SARS-CoV-2particle. In some embodiments, the composition is administered incombination with a second therapeutic agent.

Antibody Structure

Antibodies are glycoproteins with an immunoglobulin (Ig) monomericfunctional domain. Secreted antibodies can have multiple Ig units. TheIg monomer is a “Y”-shaped molecule with four polypeptide chains: twoidentical heavy chains and two identical light chains. The chains can beconnected by disulfide bonds.

There are five types of mammalian Ig heavy chains referred to as: α, δ,ε, γ, and μ, defining the class of antibody. Distinct heavy chainsdiffer in their size and composition. Each heavy chain comprises of tworegions—the constant region and the variable region. The constant regionis identical in all antibodies of the same isotype, but differs inantibodies of different isotypes. The variable region of the heavy chaindiffers in antibodies produced by different B cells, but is the same forall antibodies produced by a single B cell or a B cell clone. Thevariable region of each heavy chain is approximately 110 amino acidslong.

There are two types of light chains in mammals—lambda (λ) and kappa (κ).A light chain comprises of two domains, the constant domain and thevariable domain. The approximate length of the light chain is 211 to 217amino acids. Each antibody contains two identical light chains.

The two arms of the Y-shaped antibody molecule include the antibodybinding sites, which that can bind two antigens. The two antigens can beidentical or they can be different for example in bispecific antibodies.This region of the antibody is called the Fab (fragment, antigenbinding) region and it confers the antibody with its specificity. Thus,the Fab includes one constant and one variable domain from each heavyand each light chain of the antibody. The variable domain, also calledthe Fv region, is the most important region for recognizing and bindingto antigens such as viral proteins or receptors on the surface of hostcells. There are three variable loops light chain (VL) and threevariable loops on the heavy (VH) chain of the antibody, which areresponsible for binding to the antigen. The loops are called thecomplementarity determining regions (CDRs).

The base of the Y-shaped molecule is called the Fc (Fragment,crystallizable) region and it is important for modulating immune cellactivity. The Fc includes two heavy chains and it can bind to specificto ensure that each antibody generates an appropriate immune responsefor a particular antigen. It can also mediate different physiologicaleffects including opsonization, cell lysis, and degranulation of mastcells, basophils and eosinophils. Additionally, the two N-terminalfragments of the antibody are called the Fab region, and the C-terminalfragment is called the Fc region.

In one embodiment, the subject matter described herein relates tomonoclonal and bispecific antibodies, variants, fusion proteinscomprising an antibody portion with an antigen recognition site of therequired specificity. In some embodiments, antigen-binding fragment ofan antibody is a portion of an antibody that possesses an at least oneantigen recognition site. Fragments include for example but not limitedto Fab, Fab′, F(ab′)2 Fv), and single chain (scFv).

The antibodies can be produced recombinantly by any means known in theart. In one embodiment, such an antibody is sequenced and thepolynucleotide sequence is then cloned into a vector for expression orpropagation. In one embodiment, the antibody is synthesized. Thesequence encoding the antibody of interest may be maintained in a vectorin a host cell and the host cell can then be expanded and frozen forfuture use. The polynucleotide sequence of such antibodies may be usedfor genetic manipulation to generate the bispecific molecules describedherein.

Antibody Therapy

Antibody therapy uses monoclonal or bispecific antibodies to bind topre-determined antigens. This therapy can stimulate the patient's immunesystem to attack those antigens such as viruses. In the clinicalsetting, the most common route of administration of therapeuticantibodies is the intravenous (IV) infusion. The can be followed bysubcutaneous administration, although an intramuscular injection is alsopossible. Oral administration routes of antibodies are also beingdeveloped. The monoclonal and bispecific antibodies described herein canbe administered to a subject through any useful method known in the art.The monoclonal and bispecific antibodies described herein can beadministered daily. The monoclonal and bispecific antibodies describedherein can be administered twice, three times, four times, five times,or several times a day. The monoclonal and bispecific antibodiesdescribed herein can be administered for 1, 2, 3, 4, 5, 6 days or for 1or 2 weeks. In some embodiments, the monoclonal and bispecificantibodies described herein can be administered for a period longer thantwo weeks. The monoclonal and bispecific antibodies described herein canbe administered in combination with any other therapeutically effectiveagent or a combination of agents.

COVID-19 Therapeutics—mAbs

The only treatment currently approved for the treatment of patients withCOVID-19 is remdesivir. Remdesivir shows some benefit in shortening thetime for recovery from severe COVID-19. There is currently an effort inthe field to identify biologics or small molecules that have more potentand broad effects against the spread of the SARS-CoV-2 virus. FIG. 1Ashows a SARS-CoV-2 viral particle schematic diagram. FIG. 1B shows thespike protein trimer, the protein that located on the surface of thevirus and binds to a cell receptor on the target cells. The RBD is acritical component of the viral spike glycoprotein that is found oncoronaviruses including SARS-CoV-2 and plays the most important role inviral attachment, fusion and entry into the host cell. The receptorbinding domain (RBD) is shown in green on top. The spike protein alsohas an N-terminal domain (NTD). RBD and NTD are targeted by antibodiesagainst SARS-CoV-2 and variant strains. The spike protein trimer can beused to isolate B-cells from convalescent patient samples. FIG. 1C showsan electronic micrograph of coronavirus particles. The arrow denotes theviral spike protein on the viral membrane.

In some embodiments, the subject matter described herein relates to theisolation, characterization and providing the sequences of potentmonoclonal antibodies (mAbs) against the SARS-CoV-2 virus, which causesCOVID-19. In some embodiments, the subject matter disclosed hereindescribes the optimal COVID-19 patients from which to isolate potentmAbs against SARS-CoV-2. The mAbs can be isolated from blood samplesfrom patients diagnosed with COVID-19 or patients exhibiting COVID-19related symptoms. Once the antibody sequences are determined from thesesamples, the mAbs can be synthesized in vitro. In some embodiments, themAb sequences can be modified and optimized prior to synthesis. ThesemAb can be used for subsequent characterization experiments. In someembodiment, the subject matter disclosed herein relates to theidentification of mAbs significantly more potent, with than any otherSARS-CoV-2 mAb known in the art to date. In some embodiments, the mAblower IC50 and/or IC90 values,

The SARS-CoV-2 neutralizing mAbs described herein can be used fortreatment of subjects infected with SARS-CoV-2. In some embodiments, themAbs described herein reduce SARS-CoV-2 viral load in a subject in needthereof. In some embodiment, the mAbs described herein decrease diseaseseverity in a subject in need thereof. In some embodiments, the mAbsdescribed herein improve clinical outcome of COVID-19 in subjects inneed thereof.

In some embodiments, the mAbs described herein can be used asprophylaxis to prevent high risk subjects and individuals from becominginfected with SARS-CoV-2. In some embodiment, the high risk subject canbe healthcare workers in close proximity to COVID-19 patients or thefamily members of these healthcare workers. In some embodiment, the mAbsdescribed herein can be used as prophylaxis for the general populationat large.

Flow Through of Identification Process for the Potent COVID-19 mAbs

In one embodiment, the subject matter disclosed herein related toidentification, isolation from patients, and characterization of potentmAbs against SARS-CoV-2, its variants, or any coronavirus. Oneembodiment of the method described herein for isolation of suchantibodies is described below. In one embodiment, the subject matterdisclosed herein related to administration of the antibodies describedherein to subjects in need thereof to treat or prevent disease. In someembodiments, the treatment includes administration of one type ofmonoclonal antibody. In some embodiments, the treatment includesadministration of a cocktail of two or more monoclonal antibodies.

Plasma samples from COVID-19 patients can be isolated and evaluated forthe ability of potential antibodies contained within these plasmasamples to: A) bind the viral envelope of SARS-CoV-2 or a variant strain(analysis can be by ELISA); and B) neutralize SARS-CoV-2 or a variantstrain in vitro. Plasma samples from COVID-19 patients with severedisease or symptomology can have stronger antiviral activities thanplasma samples from COVID-19 patients with non-severe disease. Plasmasample which are determined to have the strongest activity can be usedto select patients for further analysis of monoclonal antibodies.

Peripheral blood mononuclear cells (PMBCs) can be isolated from COVID-19patients whose plasma samples exhibit the strongest activity in order toisolate single B cells. These B-cells contain mAb-sequences that can beresponsible for the strong plasma antiviral activity identified above.The antibody sequences can be recovered from these single B cells by anyhigh throughput sequencing methods known in the art. The genes from thesingle B cells encoding for these mAb sequences can be synthesized andcloned into expression vectors. The encoded monoclonal antibodies canthen be expressed in vitro and purified for subsequent analyses andcharacterization.

In vitro-produced and purified monoclonal antibodies can then tested fortheir ability to: A) bind to the virus envelope of SARS-CoV-2 or avariant strain (analysis can be by ELISA); and B) neutralize SARS-CoV-2or a variant strain, thus stopping or preventing infections caused bycoronaviruses. Neutralization analysis can be performed by bothpseudotyped virus assay and/or live virus neutralization assays. ThosemAbs that perform the best can then subjected to additionalcharacterization studies including but not limited to ELISA competitionassays, surface plasmon resonance (SPR) binding affinity analyses andsize exclusion chromatography. Antibody performance can be indicated bypotency, IC50 concentration, and IC90 concentration. An IC50 is aquantitative measure used to indicated the concentration of an antibodyneeded to inhibit a virus or a virus population by 50%. An IC90 is aquantitative measure used to indicated the concentration of an antibodyneeded to inhibit a virus or a virus population by 90%. These aremeasures of the potency of the antibody.

In one embodiment of the subject matter described herein, more than 100million cells have been screened by the described method from 8patients, 276 mAb sequences were synthesized, 66 mAbs were tested andcharacterized. In one embodiment, 6 mAbs have emerged as top hits withgood antiviral activity against SARS-CoV-2. In one embodiment, 1 mAb hasemerged with exceptional antiviral activity and potency againstSARS-CoV-2. In one embodiment, the subject matter described hereinrelates to monoclonal antibodies with significantly higher potency thanany other SARS-CoV-2 mAb known in the art to date. In one embodiment,the subject matter described herein relates to monoclonal antibodieswith significantly lower IC₅₀ and IC₉₀ concentration values than anyother mAb known in the art to date against SARS-CoV-2 or a variantstrain.

In one embodiment, additional monoclonal antibodies are identified fromthe samples in the screening pipeline and if additional plasma samplesfrom COVID-19 patient are screened for their ability to neutralizeSARS-CoV-2.

The mAbs generated through the process described herein aresignificantly more potent than other antibodies known in the art againstSARS-CoV-2 or a variant strain. In some embodiment, the subject matterdescribed herein relates to mAbs against SARS-CoV-2 with high antiviralactivity in subjects. In some embodiments the high antiviral activity ishigher than the activity of SARS-CoV-2 known in the art. In someembodiments, the subjects are humans. In some embodiments, the subjectsare human patients.

In some embodiments, more potent antibodies require smaller amounts(lower concentrations) to be administered to the subject in need thereofto achieve the desired COVID-19-related clinical effects. This can beachieved through administration of lower dosages to subjects. Thereforefewer potential side effects will be observed with less frequent dosingregimens or smaller amount of antibodies. This potentially will lowerthe antibody production costs. In some embodiments, the mAb againstSARS-CoV-2 lead to faster recovery of subjects with COVID-19 and greaterefficacy overall.

In some embodiments, the mAb described herein target multiple epitopeson the SARS-CoV-2 virus or a variant strain. In some embodiments, thesubject matter disclosed herein relates to an antibody combinationcocktails to be administered to the subject. In some embodiments, theantibodies in the cocktails target multiple epitopes on the SARS-CoV-2virus or a variant strain. In some embodiments, the antibody combinationcocktails provide even greater efficacy and lower the possibility ofviral resistance than each individual antibody of the cocktail.

In some embodiments, the mAb described herein can be used for treatmentand/or prevention of COVID-19 infection. In some embodiments, the mAbsdescribed herein can be administered to the subject as a prevention orprophylaxis. In some embodiments, the mAbs can be used for diagnosis ofCOVID-19 subject exposure. In some embodiment, the mAbs described hereincan be utilized in laboratory research and development activities.

Sequences of the mAbs Described Herein Against SARS-CoV-2 or a VariantStrain

Underlined and italicized amino acids represent the respectivecomplementarity-determining regions (CDRs). There are three CDRs persequence, appearing on the sequence in the order CDR1, CDR2, and CDR3.

In one embodiment, the monoclonal antibody 2-4 comprises SEQ ID NOs: 1and 2.

SEQ ID NO: 1 is the variable region of the heavy chain of antibodynumber 2-4.

QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPNSGGTNYTQMFQGRVTMTRDTSISTAYMEVSRLRSDDTAVYYCAR DRSWAVVYYYMDV WGKGTTVTVSS

SEQ ID NO: 2 is the variable region of the light chain of antibodynumber 2-4.

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSNN LV FGGGTKLTVL

In one embodiment, the monoclonal antibody 4-8 comprises SEQ ID NOs: 3and 4.

SEQ ID NO: 3 is the variable region of the heavy chain of antibodynumber 4-8.

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRQAPGQGLEWMG RIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDV WGQGTTVTVSS

SEQ ID NO: 4 is the variable region of the light chain of antibodynumber 4-8

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FG GGTKLTVL

In one embodiment, the monoclonal antibody 2-15 comprises SEQ ID NOs: 5and 6.

SEQ ID NO: 5 is the variable region of the heavy chain of antibodynumber 2-15.

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDI WGQGTMITVSS

SEQ ID NO: 6 is the variable region of the light chain of antibodynumber 2-15.

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADCYC SSYTSSST FV FGTGTKVTVL

In one embodiment, the monoclonal antibody 2-38 comprises SEQ ID NOs: 7and 8.

SEQ ID NO: 7 is the variable region of the heavy chain of antibodynumber 2-38.

EVQLVESGGGLVKPGGSLRLSCAASG FTFSSYSMN WVRQAPGKGLEWVS SISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCTR AGWELRLDAFDI WGQGTMVTVSS

SEQ ID NO: 8 is the variable region of the light chain of antibodynumber 2-38.

SSELTQDPAVSVALGQTVRITC QGDSLRSSYAS WYQQKPGQAPILVIY D KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYC NSRDSSGIL FG GGTKLTVL

In one embodiment, the monoclonal antibody 2-51 comprises SEQ ID NOs: 9and 10.

SEQ ID NO: 9 is the variable region of the heavy chain of antibodynumber 2-51.

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAYKSTWYFGY WGQGTLVTVSS

SEQ ID NO: 10 is the variable region of the light chain of antibodynumber 2-51.

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRM G FGGGTKLTVL

In one embodiment, the monoclonal antibody 4-32 comprises SEQ ID NOs: 11and 12.

SEQ ID NO: 11 is the variable region of the heavy chain of antibodynumber 4-32.

EVQLVESGGGLVQPGRSLRLSCAASG FSFDDYAMH WVRQAPGKGLEWVS GISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAK GLVQDYDSSGYFFADRVSAFDI WGQGTMVTVSS

SEQ ID NO: 12 is the variable region of the light chain of antibodynumber 4-32.

DIQMTQSPSSLSASVGDRVTITC RASQSINSYLN WYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTPL T F GGGTKVEIK

In one embodiment, the monoclonal antibody 2-7 comprises SEQ ID NOs: 13and 14.

SEQ ID NO: 13 is the variable region of the heavy chain of antibodynumber 2-7, which specifically recognizes the receptor binding domain(RBD).

SQITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALE WLA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYC AH HKIERIFDY WGQGTLVTVSSAS

SEQ ID NO: 14 is the variable region of the light chain of antibodynumber 2-7, which specifically recognizes the RBD.

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST V FGGGTKLTVL

In one embodiment, the monoclonal antibody 1-57 comprises SEQ ID NOs: 15and 16.

SEQ ID NO: 15 is the variable region of the heavy chain of antibodynumber 1-57, which specifically recognizes the RBD.

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDY WGQGTLVTVSS

SEQ ID NO: 16 is the variable region of the light chain of antibodynumber 1-57, which specifically recognizes the RBD.

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPST FGQGTKLEIK

In one embodiment, the monoclonal antibody 1-20 comprises SEQ ID NOs: 17and 18.

SEQ ID NO: 17 is the variable region of the heavy chain of antibodynumber 1-which specifically recognizes the RBD.

EVQLVESGGGLIQPGGSLRLSCAASG LTVSSNYMS WVRQAPGKGLEWVS VIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR D LFYYGMDV WGQGTTVTVSS

SEQ ID NO: 18 is the variable region of the light chain of antibodynumber 1-20, which specifically recognizes the RBD.

DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNSYPC FG PGTKVDIK

In one embodiment, the monoclonal antibody 2-30 comprises SEQ ID NOs: 19and 20.

SEQ ID NO: 19 is the variable region of the heavy chain of antibodynumber 2-which specifically recognizes the RBD.

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYTMH WVRQAPGKGLEWVA AISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SILYGGGMDI WGQGTTVTVSS

SEQ ID NO: 20 is the variable region of the light chain of antibodynumber 2-30, which specifically recognizes the RBD.

DIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGQAPKLLIY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNSYPL T F GGGTKVEIK

In one embodiment, the monoclonal antibody 4-20 comprises SEQ ID NOs: 21and 22.

SEQ ID NO: 21 is the variable region of the heavy chain of antibodynumber 4

20, whichs pecifically recognizesthe RBD. QVQLLQSGAEVKKPGASVKVSCKASGYSFTSYYMH WVRQAPGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDY WGQGTLVTVSS

SEQ ID NO: 22 is the variable region of the light chain of antibodynumber 4-20, which specifically recognizes the RBD.

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVT FGGGTKVEIK

In one embodiment, the monoclonal antibody 4-18 comprises SEQ ID NOs: 23and 24.

SEQ ID NO: 23 is the variable region of the heavy chain of antibodynumber 4-18, which specifically recognizes the N-Terminal domain (NTD).

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWFDP WGQGTLVTVSS

SEQ ID NO: 24 is the variable region of the light chain of antibodynumber 4-18, which specifically recognizes the NTD.

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WV FGGGTKLTVL

In one embodiment, the monoclonal antibody 5-24 comprises SEQ ID NOs: 25and 26.

SEQ ID NO: 25 is the variable region of the heavy chain of antibodynumber 5-24, which specifically recognizes the NTD.

QVQLVESGGGVVQPGRSLRLSCAASG LTFSSYVMH WVRQAPGKGLDWVGVIWYDGSKKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DPRDYYDFWSGYDYYYGLDVWGQGTTVTVSS

SEQ ID NO: 26 is the variable region of the light chain of antibodynumber 5-24, which specifically recognizes the NTD.

EIVLTQSPGILSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSGAL T FGGGTKVEIK

In one embodiment, the monoclonal antibody 5-7 comprises SEQ ID NOs: 27and 28.

SEQ ID NO: 27 is the variable region of the heavy chain of antibodynumber 5-7, which specifically recognizes the NTD.

QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG VINPSGGSTSYAEKFRGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DREPHSDSSGYWDSLKYYYYYALDVWGQGTTVTVSS

SEQ ID NO: 28 is the variable region of the light chain of antibodynumber 5-7, which specifically recognizes the NTD.

AIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPELLIY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNTYPFT F GPGTKVDIK

In one embodiment, the monoclonal antibody 1-68 comprises SEQ ID NOs: 29and 30.

SEQ ID NO: 29 is the variable region of the heavy chain of antibodynumber 1-68, which specifically recognize the NTD.

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWMG GFDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDV WGQGTTVTVSS

SEQ ID NO: 30 is the variable region of the light chain of antibodynumber 1-68, which specifically recognizes the NTD.

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YV FGTGTKVTVL

In one embodiment, the monoclonal antibody 2-43 comprises SEQ ID NOs: 31and 32.

SEQ ID NO: 31 is the variable region of the heavy chain of antibodynumber 2-43, which recognizes an epitope other than the RBD or the NTD.

QVQLVQSGAEVKKPGASVKVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPNSGGTNYAQKFQGRVTMTRDTSITTAYMELRRLRSDDTAVYYCAR GLGVGCSGGNCYLDYYYMDV WGKGTTVTVSS

SEQ ID NO: 32 is the variable region of the light chain of antibodynumber 2-43, which recognizes an epitope other than the RBD or the NTD.

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEGDYYC SSYTSSST WV FGGGTKLTVL

In one embodiment, the monoclonal antibody 4-19 comprises SEQ ID NOs: 33and 34.

SEQ ID NO: 33 is the variable region of the heavy chain of antibodynumber 4-19, which recognizes an epitope other than the RBD or the NTD.

QVQLQESGPGLVKPSETLSLTCTVSG GSISNYYWS WIRQSPGKGLEWIG YIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR S AKHWLAPPGDYYYYMDV WGKGTTVTVSS

SEQ ID NO: 34 is the variable region of the light chain of antibodynumber 4-19, which recognizes an epitope other than the RBD or the NTD.

DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNSYLT FG GGTKVEIK

In one embodiment, the monoclonal antibody 2-17 comprises SEQ ID NOs: 35and 36.

SEQ ID NO: 35 is the variable region of the heavy chain of antibodynumber 2-17, which recognizes an epitope other than the RBD or the NTD.

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GVGYRGVIPLNWFDP WGQGTVVTVSS

SEQ ID NO: 36 is the variable region of the light chain of antibodynumber 2-17, which recognizes an epitope other than the RBD or the NTD.

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFT FGGGTKVEIK

RBD Binders

In one embodiment, the monoclonal antibody 2-36 comprises SEQ ID NOs: 37and 38.

SEQ ID NO: 37 is the variable region of the heavy chain of antibodynumber 2-36, which specifically recognizes the RBD.

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLEW IG YMYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA R EVYYYDRSGYYASDGFDI WGQGTMVTVSS

SEQ ID NO: 38 is the variable region of the light chain of antibodynumber 2-36, which specifically recognizes the RBD.

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPQT FGQGTKVEIK

In one embodiment, the monoclonal antibody 1-87 comprises SEQ ID NOs: 39and 40.

SEQ ID NO: 39 is the variable region of the heavy chain of antibodynumber 1-87, which specifically recognizes the NTD.

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GIAVIGPPPSTYYYYGMDV WGQGTTVTVSS

SEQ ID NO: 40 is the variable region of the light chain of antibodynumber 1-87, which specifically recognizes the NTD.

QSALTQPASVSGSPGQSITISCTGTS SDVGGYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YV FGTGTKVTVL

In one embodiment, the monoclonal antibody 2-15mut comprises SEQ ID NOs:41 and 42.

SEQ ID NO: 41 is the variable region of the heavy chain of the 2-15mutmAb.

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDI WGQGTMITVSS

SEQ ID NO: 42 is the variable region of the light chain of the 2-15mutmAb.

QSALTQPASVSGSPGQSITISC TGTSSDVGGYN F V SWYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADSYC SSYTSSST FV FGTGTKVTVL

In one embodiment, the monoclonal antibody 4-8(39/51) comprises SEQ IDNOs: 43 and 44.

SEQ ID NO: 43 is the variable region of the heavy chain of the4-8(39/51) mAb.

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDV WGQGTTVTVSS

SEQ ID NO: 44 is the variable region of the light chain of the4-8(39/51) mAb.

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FG GGTKLTVL

In one embodiment, the monoclonal antibody 4-8(39/51/57) comprises SEQID NOs: 45 and 46.

SEQ ID NO: 45 is the variable region of the heavy chain of the4-8(39/51/57) mAb.

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGTANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDV WGQGTTVTVSS

SEQ ID NO: 46 is the variable region of the light chain of the4-8(39/51/57) mAb.

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FG GGTKLTVL

Nucleic Acid Sequences of the Monoclonal Antibodies Described HereinAgainst SARS-CoV-2 or Variant Strains

In some embodiments, the subject matter disclosed herein relates to DNAsequences that encode any of the monoclonal antibodies disclosed herein.In some embodiments, the subject matter disclosed herein relates to mRNAsequences that encode any of the antibodies disclosed herein. As usedherein, the terms “nucleic acid” and “nucleotide sequence” refer to bothDNA and RNA molecules, including base-modified, sugar-modified orbackbone-modified DNA or RNA molecules.

In some embodiments, the subject matter disclosed herein relates to anisolated nucleic acid having a nucleotide sequence encoding any of theantibodies of the present disclosure. In some embodiments, thenucleotide sequences encoding any of the antibodies of the presentdisclosure are codon-optimized for efficient expression in a hostsystem. In some embodiments, the nucleotide sequences encoding any ofthe antibodies of the present disclosure are codon-optimized to increasethe translational efficiency of the nucleotide sequences. In someembodiments, the nucleotide sequences encoding any of the antibodies ofthe present disclosure are codon-optimized to accommodate the codon biasof the host system. In some embodiments, the nucleotide sequencesencoding any of the antibodies of the present disclosure arecodon-optimized to remove redundancy and/or evolutionary constraints,including, but not limited to, the availability of tRNA isoacceptors,TATA box, Shine-Dalgarno sequences.

In some embodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 1. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 2. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 3. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 4. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 5. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 6. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 7. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 8. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 9. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 10. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 11. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 12. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 13. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 14. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 15. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 16. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 17. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 18. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 19. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 20. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 21. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 22. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 23. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 24. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 25. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 26. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 27. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 28. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 29. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 30. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 31. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 32. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 33. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 34. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 35. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 36. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 37. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 38. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 39. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 40. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 41. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 42. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 43. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 44. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 45. In someembodiments, the subject matter disclosed herein relates to acodon-optimized, isolated nucleic acid comprising a nucleic acidsequence encoding a monoclonal antibody including SEQ ID NO: 46.

In some embodiments, the subject matter disclosed herein relates to apharmaceutical composition comprising an isolated nucleic acid having anucleotide sequence encoding any of the antibodies of the presentdisclosure and a pharmaceutically acceptable carrier. In someembodiments, the subject matter disclosed herein relates to apharmaceutical composition comprising a codon-optimized, isolatednucleic acid having a nucleotide sequence encoding any of the antibodiesof the present disclosure and a pharmaceutically acceptable carrier.

COVID-19 Therapeutics with Bispecific Antibodies

Monoclonal antibodies are homogeneous in their nature of interactionwith the ligands/antigens and thereby generate an absolutemono-specificity for their target. However, sometimes this absolutespecificity for a single antigen target can result in some limitationsfor treating agents such as viruses that are known to evolve theirtarget epitopes and thereby escape from the targeting by monoclonalantibodies. To overcome such limitations, scientists have generatedantibodies which can be engineered to target multiple epitopes using asingle antibody-like molecule. These antibody-like molecules can bindtwo separate antigens at the same time and are referred to as“bispecific” antibodies. Their framework is composed of fragments of twomonoclonal antibodies whose regions have a binding affinity to twoseparate antigens. Such a framework can be useful in binding antigensthat are unconventional or rare. In some embodiments, the subject matterdescribed herein relates to generating bispecific antibodies capable ofneutralizing the SARS-CoV-2 virus and or variant strains.

The SARS-CoV-2 bispecific antibodies described herein can be used fortreatment of subjects infected with SARS-CoV-2 or a variant strain. Insome embodiments, the bispecific antibodies described herein reduceviral load in a subject in need thereof. In some embodiments, thebispecific antibodies described herein decrease disease severity in asubject in need thereof. In some embodiments, the bispecific antibodiesdescribed herein improve clinical outcome of COVID-19 in subjects inneed thereof.

In some embodiments, the bispecific antibodies described herein can beused as prophylaxis to prevent high risk subjects and individuals frombecoming infected with SARS-CoV-2 or a variant strain. In someembodiments, the high risk subject can be healthcare workers in closeproximity to COVID-19 patients or the family members of these healthcareworkers. In some embodiments, the bispecific antibodies described hereincan be used as prophylaxis for the general population at large.

In some embodiments, more potent antibodies require smaller amounts tobe administered to the subject to achieve the desired COVID-19-relatedrecovery effects. This can be through lower dosages administered to thesubjects and therefore less potential side effects, less frequent dosingregimens, or lower antibody production costs. In some embodiments,potency is measured by IC50 and IC90 concentration values.

In some embodiments, the bispecific antibodies described herein targetmultiple epitopes on the SARS-CoV-2 virus or a variant strain. In someembodiments, the subject matter disclosed herein relates to bispecificantibody combination cocktails. In some embodiments, the antibodies inthe cocktails target multiple epitopes on the SARS-CoV-2 virus or avariant strain. In some embodiments, the bispecific antibody combinationcocktails provide even greater efficacy and lower the possibility ofviral resistance than each individual antibody of the cocktail. In someembodiments, the bispecific antibodies described herein can be utilizedin laboratory research and development activities. In one embodiment,the bispecific antibodies describe herein includes the variable regionsof a first and a second antibody, in which the first antibody binds toan epitope on the receptor binding domain (RBD) of the coronavirus,while the second binds to an epitope on the N-terminal domain (NTD) ofthe coronavirus.

Pairing the anti-RBD and the anti-NTD domain antibodies in such abispecific format would mainly provide for increasing the geneticbarrier for the virus to achieve resistance against the antibodies. Italso allows clinical practitioners to only administer a singleformulation of one bispecific antibody to patients thereby simplifyingtreatment. In some embodiments, the bispecific antibodies areadministered in a cocktail of two or more antibodies. As for marketingand supply chain benefits, bispecific antibodies present an economicalalternative to producing in a single molecule format, those combinationsof monoclonal antibodies known to increase the threshold of resistanceto SARS-CoV-2.

In one embodiment, the subject matter disclosed herein relates tobispecific antibodies engineered for treatment and prevention ofCOVID-19 infections. Engineered bispecific antibodies can combine thebinding specificity of two antibodies in only one molecule. Bispecificantibodies can recognize two antigens on different cells or on the samecell. Thus, by virtue of specifically binding the two antigens,engineered bispecific antibodies can bring two cells in close proximityor activate two receptors simultaneously. Additionally, blocking twotarget proteins with one antibody instead of two may be more efficient.In some embodiments, bispecific antibodies can target two viral epitopesproviding higher barrier for viral escape. In some embodiments,bispecific antibodies can have synergetic effect on potency against theviral target.

In one embodiment, the engineered antibodies achieve bispecificity usingthe CrossMab format (Schaefer, 2011). The CrossMab engineering formatallows for the bispecific antibody to adopt a more native antibody-likestructure. This can facilitate binding of the bispecific antibody toweakly-expressed antigens, while avoiding overstimulation of immuneresponses. In some embodiments, bispecific antibodies in the CrossMabformat can be anchored to a host cell membrane. This allows for improvedlocal antibody concentration, targeting of sequential and/orinterdependent virus entry steps, and compensating for monovalentbinding.

As described herein, the CrossMab format for engineering bispecificantibodies can be utilized to engineer bispecific antibodies against theSARS-CoV-2 virus or a variant strain. As shown in FIG. 41 , the creationof a “knob” in one heavy chain and a “hole” in the other heavy chain ofthe bispecific antibody favors the formation of heavy chainheterodimers, while the “crossover” of CL and CH1 sequences (theconstant domains, heavy and light chains) in one arm of the antibodyfavors correct Heavy-Light chain pairings in both arms. The CrossMabformat allows for correct assembly of two heavy chains and two lightchains from different parental antibodies into one bispecific antibodymolecule that resembles a typical monoclonal antibody in terms of massand architecture, and with no artificial linkers required. Each antibodyarm can be selected from different potent neutralizing antibodiesagainst SARS-CoV-2 or a variant strain. Other bispecific formats thatbring together the particular SARS-CoV-2 antibody combinations describedherein can yield similar neutralization activities. As shown in FIG. 41, human IgG isotype 1 Fc can be engineered for reduced Fc-effectorfunction with the L234F, L235E and P331S mutations and for half-lifewith the M428L and N434S mutations.

In one embodiment, the bispecific antibody comprises two polypeptidechains, one from each parental monoclonal antibody. In one embodiment,the first parental polypeptide arm comprises the light chain and theheavy chain polypeptides of the first parental antibody. The light chaincan include the light chain variable domain (VL) comprising the lightchain binding region and the light chain constant domain (CL) if thefirst parental antibody. The heavy chain can include the heavy chainvariable domain (VH) comprising the heavy chain binding region and theheavy chain constant domain (CH) of the first parental antibody. In oneembodiment, the first parental polypeptide arm also includes a domain,which promotes heterodimerization with the second polypeptide. In oneembodiment, this heterodimerization domain can covalently bond the firstparental polypeptide to the second parental polypeptide of thebispecific antibody.

In one embodiment, the second parental polypeptide arm comprises a lightchain and a heavy chain polypeptides of the second parental antibody.The light chain can include the light chain variable domain (VL)comprising the light chain binding region and the light chain constantdomain (CL) of the second parental antibody. The heavy chain can includethe heavy chain variable domain (VH) comprising the heavy chain bindingregion and the heavy chain constant domain (CH) of the second parentalantibody. In one embodiment, the second parental polypeptide arm alsoincludes a domain, which promotes heterodimerization with the secondpolypeptide. In one embodiment, this heterodimerization domain cancovalently bond the first parental polypeptide to the second parentalpolypeptide of the bispecific antibody. In one embodiment, thebispecific antibody further comprises linkers and disulfide bondsconnecting the two parental polypeptides of the antibody. The linkerscan be any suitable sequence of amino acids. In one embodiment, the

The bispecific antibodies described herein include the variable regionsof a first and a second antibody, in which the first antibody binds toan epitope on the receptor binding domain (RBD) of the coronavirus andis selected from 8 monoclonal Abs (1-20, 1-57, 2-7, 2-2-30, 2-36, 2-43and 4-20) while the second binds to an epitope on the N-terminal domain(NTD) of the coronavirus and is also selected from 8 monoclonal Abs(1-68, 1-87, 2-17, 2-51, 4-8, 4-18, 4-19 and 5-24).

The CrossMabs described herein utilize human IgG isotype 1 Fc backbone.The backbone can have additional mutations engineered for reducedFc-effector function with the L234F, L235E and P331S mutations and forhalf-life with the M428L and N434S mutations.

In order to generate bispecific antibodies that would meet these goals,58 candidate bispecific Abs were screened for their potency againstSARS-CoV-2 live infectious virus using an in vitro assay. Briefly,purified candidate bispecific Ab was mixed with infectious live virusfor 60 min and then added to a monolayer of Vero E6 cells to measure theextent of neutralization. Antibodies were diluted 5 fold from 10 μg/mLwhile virus was incubated with cells at MOI=0.1. Three days postinfection, the cells were measured for the cytopathic effects induced bythe live virus replication. Difference in the extent of infection fromthe control wells bearing no antibodies was converted to percentage andthe value for inhibition of 50% of the virus (IC50) and 90% of the virus(IC90) was calculated using non-linear regression analysis.

Using the potency values, the bispecific antibodies of merit werenominated based on their fold enhancement of the IC₉₀ concentrationsthat they achieved in comparison to their parental antibodies.Bispecific antibodies that had a potency with IC₅₀≤10 ng/mL and withIC₉₀≤50 ng/mL were chosen as the ones that would be capable of achievingthe greatest barrier to resistance by SARS-CoV-2. Ab X and Ab Y areirrelevant single arm Fab controls. Selected bispecific antibodycandidates achieve similar potency as co-administration of the twoparental mAbs.

SARS-CoV-2 Variant Strains

In some embodiments, the bispecific antibodies exhibit neutralizationactivity against wild-type SARS-CoV-2 virus (WA1). In some embodiments,the bispecific antibodies exhibit neutralization activity againstSARS-CoV-2 variants. In some embodiments, the bispecific antibodiesdisclosed herein show potent neutralization activities againstSARS-CoV-2 wild-type and multiple variant virus strains. In someembodiments, the SARS-CoV-2 variants are B.1.1.7 (UK variant), B.1.351(SA variant), B.1.526 (NY variant), or P.1 (Brazil variant).

In one embodiment, each arm of the bispecific antibody constructed isselected from 19 potent neutralizing antibodies against SARS-CoV-2.Additional bispecific antibodies 2-7/5-7, 2-7/1-57 and the CrossMabformats with reverse the knob and hole arms, namely 5-7/2-7 or 1-57/2-7,showed high potencies when tested against the wild-type virus. As 1-57activity can be impacted by SARS-CoV-2 variant containing L452R mutation(such as California variant), which crashes mAb 1-57 heavy chain bindingsuggested by structural modeling, 2-7/5-7 was down-selected asdevelopment candidate and further characterized by neutralizationagainst SARS-CoV-2 variants and showed potent neutralization against newemerging variants such as B.1.1.7 (UK variant), B.1.351 (SA variant),B.1.526 (NY variant) and P.1 (BZ variant). For many of the bispecificantibodies tested herein, both arms of the bispecific antibodiescontribute to the neutralization activity of the bispecific molecule.These bispecific antibodies with potent neutralization activitiesagainst SARS-CoV-2 and the variants offer new therapeutics for thetreatment and prevention of COVID-19, as a single antibody molecule toprovide a higher genetic barrier for viral escape and lower cost thanantibody combination. We expect the activity enhancement observed can beextended to other engineered bispecific antibody format.

Antibody Sequences for Bispecific Antibodies

Underlined and italicized amino acids represent the respectivecomplementarity-determining regions (CDRs). There are three CDRs persequence, appearing on the sequence in the order CDR1, CDR2, and CDR3.

The 2-17/2-7 bispecific antibody sequence can comprise:

SEQ ID NO: 47 is the amino acid sequence defining the 2-17 derived heavychain of the 2-17/2-7 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GVGYRGVIPLNWFDPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 48 is the amino acid sequence defining the 2-17 derived Lightchain of the 2-17/2-7 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 49 is the amino acid sequence defining the 2-7 derived heavychain of the 2-17/2-7 antibody 2-7HC-Knob

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQK SLSLSPGK

SEQ ID NO: 50 is the amino acid sequence defining the 2-7 derived lightchain of the 2-17/2-7 antibody 2-7LC

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST VFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS

The 1-57/5-7 bispecific antibody sequence can comprise:

SEQ ID NO: 51 is the amino acid sequence defining the 1-57 derived heavychain of the 1-57/5-7 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 52 is the amino acid sequence defining the 1-57 derived lightchain of the 1-57/5-7 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 53 is the amino acid sequence defining the 5-7 derived heavychain of the 1-57/5-7 antibody 5-7 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG V INPSGGSTSYAEKFRGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DR EPHSDSSGYWDSLKYYYYYALDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 54 is the amino acid sequence defining the 5-7 derived lightchain of the 1-57/5-7 antibody 5-7LC

AIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPELLIY A ASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNTYPFT FGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC

The 5-7/1-57 bispecific antibody sequence can comprise:

SEQ ID NO: 55 is the amino acid sequence defining the 5-7 derived heavychain of the 5-7/1-57 antibody 5-7HC-Hole-Cross

QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG V INPSGGSTSYAEKFRGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DR EPHSDSSGYWDSLKYYYYYALDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLH EALHSHYTQKSLSLSPGK

SEQ ID NO: 56 is the amino acid sequence defining the 5-7 derived Lightchain of the 5-7/1-57 antibody 5-7VLCH1

AIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPELLIY A ASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNTYPFT FGPGTKVDIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSC

SEQ ID NO: 57 is the amino acid sequence defining the 1-57 derived heavychain of the 5-7/1-57 antibody 1-57HC-Knob

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG R TRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYCAR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 58 is the amino acid sequence defining the 1-57 derived lightchain of the 5-7/1-57 antibody 1-57LC

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPST FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC

The 2-7/5-7 bispecific antibody sequence can comprise:

SEQ ID NO: 59 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/5-7 antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVG VGWIRQPPGKALEWL A LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAH H KIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLS PGK

SEQ ID NO: 60 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/5-7 antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLMI Y DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSSTV FGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSC

SEQ ID NO: 61 is the amino acid sequence defining the 5-7 derived heavychain of the 2-7/5-7 antibody 5-7 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG V INPSGGSTSYAEKFRGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DR EPHSDSSGYWDSLKYYYYYALDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 62 is the amino acid sequence defining the 5-7 derived lightchain of the 2-7/5-7 antibody 5-7LC

AIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPELLIY A ASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNTYPFT FGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG LSSPVTKSFNRGEC

The 5-7/2-7 bispecific antibody sequence can comprise:

SEQ ID NO: 63 is the amino acid sequence defining the 5-7 derived heavychain of the 5-7/2-7 antibody 5-7HC-Hole-Cross

QVQLVQSGAEVKKPGASVKVSCKASG YTFTSYYMH WVRQAPGQGLEWMG V INPSGGSTSYAEKFRGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DR EPHSDSSGYWDSLKYYYYYALDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLH EALHSHYTQKSLSLSPGK

SEQ ID NO: 64 is the amino acid sequence defining the 5-7 derived Lightchain of the 5-7/2-7 antibody 5-7VLCH1

AIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPELLIY A ASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNTYPFT FGPGTKVDIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSC

SEQ ID NO: 65 is the amino acid sequence defining the 2-7 derived heavychain of the 5-7/2-7 antibody 2-7HC-Knob

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVG VGWIRQPPGKALEWL A LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAH H KIERIFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 66 is the amino acid sequence defining the 2-7 derived lightchain of the 5-7/2-7 antibody 2-7LC

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLMI Y DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSSTV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTH EGSTVEKTVAPTECS

The 2-17/1-57 bispecific antibody sequence can comprise:

SEQ ID NO: 67 is the amino acid sequence defining the 2-17 derived heavychain of the 2-17/1-57 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG G NIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GV GYRGVIPLNWFDPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQK SLSLSPGK

SEQ ID NO: 68 is the amino acid sequence defining the 2-17 derived lightchain of the 2-17/1-57 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 69 is the amino acid sequence defining the 1-57 derived heavychain of the 2-17/1-57 antibody 1-57HC-Knob

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVL HEALHSHYTQKSLSLSPGK

SEQ ID NO: 70 is the amino acid sequence defining the 1-57 derived lightchain of the 2-17/1-57 antibody 1-57LC

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC

The 2-17/2-15 bispecific antibody sequence can comprise:

SEQ ID NO: 71 is the amino acid sequence defining the 2-17 derived heavychain of the 2-17/2-15 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFG T ANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GVGYRGVIPLNWFDPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 72 is the amino acid sequence defining the 2-17 derived lightchain of the 2-17/2-15 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 73 is the amino acid sequence defining the 2-15 derived heavychain of the 2-17/2-15 antibody 2-15HC-Knob

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDIWGQGTMITVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLH EALHSHYTQKSLSLSPGK

SEQ ID NO: 74 is the amino acid sequence defining the 2-15 derived lightchain of the 2-17/2-15 antibody 2-15LC

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADCYC SSYTSSST FVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-17/2-30 bispecific antibody sequence can comprise:

SEQ ID NO: 75 is the amino acid sequence defining the 2-17 derived heavychain of the 2-17/2-30 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GVGYRGVIPLNWFDPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 76 is the amino acid sequence defining the 2-17 derived lightchain of the 2-17/2-30 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 77 is the amino acid sequence defining the 2-30 derived heavychain of the 2-17/2-30 antibody 2-30 HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FT F SSYTMH WVRQAPGKGLEWVA AISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SILYGGGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQK SLSLSPGK

SEQ ID NO: 78 is the amino acid sequence defining the 2-30 derived lightchain of the 2-17/2-30 antibody 2-30 LC

DIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGQAPKLLIY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNSYPLT FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV THQGLSSPVTKSFNRGEC

The 2-17/4-20 bispecific antibody sequence can comprise:

SEQ ID NO: 79 is the amino acid sequence defining the 2-17 derived heavychain of the 2-17/4-20 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GVGYRGVIPLNWFDPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 80 is the amino acid sequence defining the 2-17 derived lightchain of the 2-17/4-20 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 81 is the amino acid sequence defining the 4-20 derived heavychain of the 2-17/4-20 antibody 4-20 HC-Knob

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQ KSLSLSPGK

SEQ ID NO: 82 is the amino acid sequence defining the 4-20 derived lightchain of the 2-17/4-20 antibody 4-20 LC

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC

The 5-24/1-57 bispecific antibody sequence can comprise:

SEQ ID NO: 83 is the amino acid sequence defining the 5-24 derived heavychain of the 5-24/1-57 antibody 5-24HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG LTFSSYVMH WVRQA PGKGLDWVG VIWYDGSKKYYADSVKGRFTISRDNSKNTLY LQMNSLRAEDTAVYYCAR DPRDYYDFWSGYDYYYGLDV WGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFS CSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 84 is the amino acid sequence defining the 5-24 derived lightchain of the 5-24/1-57 antibody 5-24VLCH1

EIVLTQSPGILSLSPGERATLSC RASQSVSSSYLA WYQQK PGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLE PEDFAVYYC QQYGSSGALT FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSC

SEQ ID NO: 85 is the amino acid sequence defining the 1-57 derived heavychain of the 5-24/1-57 antibody 1-57HC-Knob

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQA PGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNS LYLQMNSLKTEDTAVYYCAR VHRWAYCINGVCFGAYSDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV LHEALHSHYTQKSLSLSPGK

SEQ ID NO: 86 is the amino acid sequence defining the 1-57 derived lightchain of the 5-24/1-57 antibody 1-57LC

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQK PGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLE PEDFAVYYC QQYGSSPST FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC

The 5-24/2-15 bispecific antibody sequence can comprise:

SEQ ID NO: 87 is the amino acid sequence defining the 5-24 derived heavychain of the 5-24/2-15 antibody 5-24HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG LT F SSYVMH WVRQA PGKGLDWVG VIWYDGSKKYYADSVKGRFTISRDNSKNTLY LQMNSLRAEDTAVYYCAR DPRDYYDFWSGYDYYYGLDV WGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFS CSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 88 is the amino acid sequence defining the 5-24 derived lightchain of the 5-24/2-15 antibody 5-24VLCH1

EIVLTQSPGILSLSPGERATLSC RASQSVSSSYLA WYQQK PGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLE PEDFAVYYC QQYGSSGALT FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSC

SEQ ID NO: 89 is the amino acid sequence defining the 2-15 derived heavychain of the 5-24/2-15 antibody 2-15HC-Knob

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQA PGQGLEWMGWINPISDGTNYAQKFQGWVTMTRDTSISTVY MELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDI WGQGTMITVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVL HEALHSHYTQKSLSLSPGK

SEQ ID NO: 90 is the amino acid sequence defining the 2-15 derived lightchain of the 5-24/2-15 antibody 2-15LC

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQ HPGKAPKLMIY DVSKRPSGVSNRFSGSKSGNTASLTISGL QAEDEADCYC SSYTSSSTFV FGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 5-24/4-20 bispecific antibody sequence can comprise:

SEQ ID NO: 91 is the amino acid sequence defining the 5-24 derived heavychain of the 5-24/4-20 antibody 5-24HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG LTFSSYVMH WVRQA PGKGLDWVG VIWYDGSKKYYADSVKGRFTISRDNSKNTLY LQMNSLRAEDTAVYYCA RDPRDYYDEWSGYDYYYGLDV WGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFS CSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 92 is the amino acid sequence defining the 5-24 derived lightchain of the 5-24/4-20 antibody 5-24VLCH1

EIVLTQSPGILSLSPGERATLSC RASQSVSSSYLA WYQQK PGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLE PEDFAVYYC QQYGSSGALT FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSC

SEQ ID NO: 93 is the amino acid sequence defining the 4-20 derived heavychain of the 5-24/4-20 antibody 4-20HC-Knob

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQA PGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVY MELSSLRSEDTAVYYCAR PGGGSYQEFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 94 is the amino acid sequence defining the 4-20 derived lightchain of the 5-24/4-20 antibody 4-20LC

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKP GKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQP EDFATYYC QQSYNTLQVT FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ GLSSPVTKSFNRGEC

The 1-20/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 95 is the amino acid sequence defining the 1-20 derived heavychain of the 1-20/1-68 antibody 1-20HC-Hole-Cross

EVQLVESGGGLIQPGGSLRLSCAASG LTVSSNYMS WVRQA PGKGLEWVS VIYSGGSTEYADSVKGRFTISRDNSKNTLYL QMNSLRAEDTAVYYCAR DLFYYGMDV WGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 96 is the amino acid sequence defining the 1-20 derived lightchain of the 1-20/1-68 antibody 1-20VLCH1

DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQQKP GKAPKLLIY AASTLQSGVPSRFSGSGSGTEFTLTISSLQP EDFATYYC QQLNSYPC FGPGTKVDIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSC

SEQ ID NO: 97 is the amino acid sequence defining the 1-68 derived heavychain of the 1-20/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQA PGKG LEWMGGEDPEDAETIYAQKFQGRVTMTEDTSTDTAY MELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDV WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLH EALHSHYTQKSLSLSPGK

SEQ ID NO: 98 is the amino acid sequence defining the 1-68 derived lightchain of the 1-20/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 1-20/2-17 bispecific antibody sequence can comprise:

SEQ ID NO: 99 is the amino acid sequence defining the 1-20 derived heavychain of the 1-20/2-17 antibody 1-20HC-Hole-Cross

EVQLVESGGGLIQPGGSLRLSCAASG LTVSSNYMS WVRQAPGKGLEWVS VIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR D LFYYGMD VWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 100 is the amino acid sequence defining the 1-20 derivedlight chain of the 1-20/2-17 antibody 1-20VLCH1

DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNSYPC FGPGTKVDIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSC

SEQ ID NO: 101 is the amino acid sequence defining the 2-17 derivedheavy chain of the 1-20/2-17 antibody 2-17HC-Knob

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR GVGYRGVIPLNWFDPWGQGTVVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHS HYTQKSLSLSPGK

SEQ ID NO: 102 is the amino acid sequence defining the 2-17 derivedlight chain of the 1-20/2-17 antibody 2-17LC

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC

The 1-20/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 103 is the amino acid sequence defining the 1-20 derivedheavy chain of the 1-20/4-18 antibody 1-20HC-Hole-Cross

EVQLVESGGGLIQPGGSLRLSCAASG LTVSSNYMS WVRQAPGKGLEWVS VIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR D LFYYGMDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 104 is the amino acid sequence defining the 1-20 derivedlight chain of the 1-20/4-18 antibody 1-20VLCH1

DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNSYPC FGPGTKVDIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSC

SEQ ID NO: 105 is the amino acid sequence defining the 4-18 derivedheavy chain of the 1-20/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 106 is the amino acid sequence defining the 4-18 derivedlight chain of the 1-20/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 1-20/5-24 bispecific antibody sequence can comprise: SEQ ID NO: 107is the amino acid sequence defining the 1-20 derived heavy

chainofthe1-20/5-24antibody1-20HC-Hole-Cross EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMS WVRQAPGKGLEWVS VIYSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR D LFYYGMDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 108 is the amino acid sequence defining the 1-20 derivedlight chain of the 1-20/5-24 antibody 1-20VLCH1

DIQLTQSPSFLSASVGDRVTITC RASQGISSYLA WYQQKPGKAPKLLIY AASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYC QQLNSYPC FGPGTKVDIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSC

SEQ ID NO: 109 is the amino acid sequence defining the 5-24 derivedheavy chain of the 1-20/5-24 antibody 5-24HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG LTFSSYVMH WVRQAPGKGLDWVG VIWYDGSKKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DPRDYYDFWSGYDYYYGLDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLH EALHSHYTQKSLSLSPGK

SEQ ID NO: 110 is the amino acid sequence defining the 5-24 derivedlight chain of the 1-20/5-24 antibody 5-24LC

EIVLTQSPGILSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSGAL TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC EVTHQGLSSPVTKSFNRGEC

Bispecific Antibodies with Both LALA (TM) and LS Mutations:

The 2-7/4-8(39/51/57) bispecific antibody sequence can comprise:

SEQ ID NO: 111 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/4-8(39/51/57) antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG F SLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 112 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/4-8(39/51/57) antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST VFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSC

SEQ ID NO: 113 is the amino acid sequence defining the 4-8(39/51/57)derived heavy chain of the 2-7/4-8(39/51/57) antibody 4-8(39/51/57)HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGTANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 114 is the amino acid sequence defining the 4-8(39/51/57)derived light chain of the 2-7/4-8(39/51/57) antibody 4-8LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 2-17/2-36 bispecific antibody sequence can comprise:

SEQ ID NO: 115 is the amino acid sequence defining the 2-17 derivedheavy chain of the 2-17/2-36 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWMG GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCA R GVGYRGVIPLNW F DPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 116 is the amino acid sequence defining the 2-17 derivedlight chain of the 2-17/2-36 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLIY GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPPFTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 117 is the amino acid sequence defining the 2-36 derivedheavy chain of the 2-17/2-36 antibody 2-36HC-Knob

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLEW IG YMYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA R EVYYYDRSGYYASDGFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 118 is the amino acid sequence defining the 2-36 derivedlight chain of the 2-17/2-36 antibody 2-36LC

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPQTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE VTHQGLSSPVTKSFNRGEC

The 2-36/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 119 is the amino acid sequence defining the 2-36 derivedheavy chain of the 2-36/1-68 antibody 2-36HC-Hole-Cross

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLEW IG YMYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA R EVYYYDRSGYYASDGFDIWGQGTMVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCS VLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 120 is the amino acid sequence defining the 2-36 derivedlight chain of the 2-36/1-68 antibody 2-36VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPQTFGQGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 121 is the amino acid sequence defining the 1-68 derivedheavy chain of the 2-36/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWMG G F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 122 is the amino acid sequence defining the 1-68 derivedlight chain of the 2-36/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-36/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 123 is the amino acid sequence defining the 2-36 derivedheavy chain of the 2-36/4-18 antibody 2-36HC-Hole-Cross

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLEW IG YMYYSGSTKYNPS LKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA R EVYYYDRSGYYASDGFDIWGQGTMVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCS VLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 124 is the amino acid sequence defining the 2-36 derivedlight chain of the 2-36/4-18 antibody 2-36VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPQTFGQGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 125 is the amino acid sequence defining the 4-18 derivedheavy chain of the 2-36/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FT F SSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 126 is the amino acid sequence defining the 4-18 derivedlight chain of the 2-36/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-30/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 127 is the amino acid sequence defining the 2-30 derivedheavy chain of the 2-30/1-68 antibody 2-30HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG FT F SSYTMH WVRQAPGKGLEWVA AISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SILYGGGMDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 128 is the amino acid sequence defining the 2-30 derivedlight chain of the 2-30/1-68 antibody 2-30VLCH1

DIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGQAPKLLIY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNSYPLI FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSC

SEQ ID NO: 129 is the amino acid sequence defining the 1-68 derivedheavy chain of the 2-30/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWMG GFDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 130 is the amino acid sequence defining the 1-68 derivedlight chain of the 2-30/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-30/4-18 bispecific antibody can comprise:

SEQ ID NO: 131 is the amino acid sequence defining the 2-30 derivedheavy chain of the 2-30/4-18 antibody 2-30HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYTMH WVRQAPGKGLEWVA AISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SILYGGGMDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 132 is the amino acid sequence defining the 2-30 derivedlight chain of the 2-30/4-18 antibody 2-30VLCH1

DIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGQAPKLLIY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNSYPL T FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSC

SEQ ID NO: 133 is the amino acid sequence defining the 4-18 derivedheavy chain of the 2-30/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAAS GFTFSSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSW F DPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 134 is the amino acid sequence defining the 4-18 derivedlight chain of the 2-30/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-7/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 135 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/4-8(39/51) antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 136 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/4-8(39/51) antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST VFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSC

SEQ ID NO: 137 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 2-7/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GT F SSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 138 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 2-7/4-8(39/51) antibody 4-8LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 1-57/1-87 bispecific antibody sequence can comprise:

SEQ ID NO: 139 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/1-87 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG F T F SDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 140 amino acid sequence defining the 1-57 derived light chainof the 1-57/1-87 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 141 is the amino acid sequence defining the 1-87 derivedheavy chain of the 1-57/1-87 antibody 1-87HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GIAVIGPPPSTYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 142 is the amino acid sequence defining the 1-87 derivedlight chain of the 1-57/1-87 antibody 1-87LC

QSALTQPASVSGSPGQSITISCTGTS SDVGGYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 1-57/4-8(39/51) bispecific antibody can comprise:

SEQ ID NO: 143 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/4-8(39/51) antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 144 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/4-8(39/51) antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 145 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 1-57/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 146 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 1-57/4-8(39/51) antibody 4-8(39/51)LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 2-7/2-51 bispecific antibody:

SEQ ID NO: 147 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/2-51 antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG F SLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 148 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/2-51 antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST VFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSC

SEQ ID NO: 149 is the amino acid sequence defining the 2-51 derivedheavy chain of the 2-7/2-51 antibody 2-51 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG GFDPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAYKSTWYFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 150 is the amino acid sequence defining the 2-51 derivedlight chain of the 2-7/2-51 antibody 2-51LC

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRM GFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS

The 2-15/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 151 is the amino acid sequence defining the 2-15 derivedheavy chain of the 2-15/4-8(39/51) antibody 2-15HC-Hole-Cross

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWA YDAFDIWGQGTMITVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSC SVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 152 is the amino acid sequence defining the 2-15 derivedlight chain of the 2-15/4-8(39/51) antibody 2-15VLCH1

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADCYC SSYTSSST FVFGTGTKVTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSC

SEQ ID NO: 153 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 2-15/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 154 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 2-15/4-8(39/51) antibody 4-8(39/51)LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 1-57/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 155 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/4-18 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 156 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/4-18 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 157 is the amino acid sequence defining the 4-18 derivedheavy chain of the 1-57/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FT F SSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 158 is the amino acid sequence defining the 4-18 derivedlight chain of the 1-57/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-7/1-68 bispecific antibody can comprise:

SEQ ID NO: 159 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/1-68 antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 160 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/1-68 antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST VFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSC

SEQ ID NO: 161 is the amino acid sequence defining the 1-68 derivedheavy chain of the 2-7/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSGYTLIELSMHWVRQAPGKG LEWMG G F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 162 is the amino acid sequence defining the 1-68 derivedlight chain of the 2-7/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 4-20/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 163 is the amino acid sequence defining the 4-20 derivedheavy chain of the 4-20/4-18 antibody 4-20HC-Hole-Cross

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHS HYTQKSLSLSPGK

SEQ ID NO: 164 is the amino acid sequence defining the 4-20 derivedlight chain of the 4-20/4-18 antibody 4-20VLCH1

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 165 is the amino acid sequence defining the 4-18 derivedheavy chain of the 4-20/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAAS GFT F SSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 166 is the amino acid sequence defining the 4-18 derivedlight chain of the 4-20/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-15mut/2-51 bispecific antibody sequence can comprise:

SEQ ID NO: 167 is the amino acid sequence defining the 2-15mut derivedheavy chain of the 2-15mut/2-51 antibody 2-15HC-Hole-Cross

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDIWGQGTMITVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSC SVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 168 is the amino acid sequence defining the 2-15mut derivedlight chain of the 2-15mut/2-51 antibody 2-15mutVLCH1

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADSYC SSYTSSST FVFGTGTKVTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSC

SEQ ID NO: 169 is the amino acid sequence defining the 2-51 derivedheavy chain of the 2-15mut/2-51 antibody 2-51 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG GFDPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAYKSTWYFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 170 is the amino acid sequence defining the 2-51 derivedlight chain of the 2-15mut/2-51 antibody 2-51LC

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRM GFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS

The 4-20/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 171 is the amino acid sequence defining the 4-20 derivedheavy chain of the 4-20/4-8(39/51) antibody 4-20HC-Hole-Cross

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG I INPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHS HYTQKSLSLSPGK

SEQ ID NO: 172 is the amino acid sequence defining the 4-20 derivedlight chain of the 4-20/4-8(39/51) antibody 4-20VLCH1

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 173 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 4-20/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 174 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 4-20/4-8(39/51) antibody 4-8(39/51)LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 1-57/2-51 bispecific antibody sequence can comprise:

SEQ ID NO: 175 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/2-51 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 176 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/2-51 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 177 is the amino acid sequence defining the 2-51 derivedheavy chain of the 1-57/2-51 antibody 2-51 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAYKSTWYFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 178 is the amino acid sequence defining the 2-51 derivedlight chain of the 1-57/2-51 antibody 2-51LC

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRM GFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS

The 4-20/1-87 bispecific antibody sequence can comprise:

SEQ ID NO: 179 is the amino acid sequence defining the 4-20 derivedheavy chain of the 4-20/1-87 antibody 4-20HC-Hole-Cross

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHS HYTQKSLSLSPGK

SEQ ID NO: 180 is the amino acid sequence defining the 4-20 derivedlight chain of the 4-20/1-87 antibody 4-20VLCH1

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 181 is the amino acid sequence defining the 1-87 derivedheavy chain of the 4-20/1-87 antibody 1-87HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GIAVIGPPPSTYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEA LHSHYTQKSLSLSPGK

SEQ ID NO: 182 is the amino acid sequence defining the 1-87 derivedlight chain of the 4-20/1-87 antibody 1-87LC

QSALTQPASVSGSPGQSITISCTGTS SDVGGYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 1-57/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 183 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/1-68 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 184 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/1-68 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 185 is the amino acid sequence defining the 1-68 derivedheavy chain of the 1-57/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWMG GEDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 186 is the amino acid sequence defining the 1-68 derivedlight chain of the 1-57/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

Bispecific Antibodies with LS Mutations Only

The 2-7/4-8(39/51/57) bispecific antibody sequence can comprise:

SEQ ID NO: 187 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/4-8(39/51/57) antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG F SLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 188 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/4-8(39/51/57) antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKL MIY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTS STVFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 189 is the amino acid sequence defining the 4-8(39/51/57)derived heavy chain of the 2-7/4-8(39/51/57) antibody 4-8(39/51/57)HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWM G RNIPILGTANYA Q KF QG RVTITADKSTSTAYMELSSLRSEDTAVYYC AS L Q TVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 190 is the amino acid sequence defining the 4-8(39/51/57)derived light chain of the 2-7/4-8(39/51/57) antibody 4-8LC

SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY QDNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-17/2-36 bispecific antibody sequence can comprise:

SEQ ID NO: 191 is the amino acid sequence defining the 2-17 derivedheavy chain of the 2-17/2-36 antibody 2-17HC-Hole-Cross

QVQLVQSGAEVKKPGSSVKVSCKASG GTFSSYAIS WVRQAPGQGLEWM G GNIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC AR GVGYRGVIPLNW F DPWGQGTVVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 192 is the amino acid sequence defining the 2-17 derivedlight chain of the 2-17/2-36 antibody 2-17VLCH1

EIVMTQSPATLSVSPGERATLSC RASQSVSSDLA WYQHKPGQAPRLLI Y GASTRATGIPVRFSGSGSGTEFTLTISSLQSEDFAVYYC QQYNNWPP FTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 193 is the amino acid sequence defining the 2-36 derivedheavy chain of the 2-17/2-36 antibody 2-36HC-Knob

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLE WIG YMYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY CAR EVYYYDRSGYYASDGFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 194 is the amino acid sequence defining the 2-36 derivedlight chain of the 2-17/2-36 antibody 2-36LC

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLL IY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSP QTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV YACEVTHQGLSSPVTKSFNRGEC

The 2-36/1-68 bispecific antibody sequence:

SEQ ID NO: 195 is the amino acid sequence defining the 2-36 derivedheavy chain of the 2-36/1-68 antibody 2-36HC-Hole-Cross

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLE WIG YMYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY CAR EVYYYDRSGYYASDGFDIWGQGTMVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 196 is the amino acid sequence defining the 2-36 derivedlight chain of the 2-36/1-68 antibody 2-36VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLL IY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSP QTFGQGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 197 is the amino acid sequence defining the 1-68 derivedheavy chain of the 2-36/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWM GG F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYC AT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 198 is the amino acid sequence defining the 1-68 derivedlight chain of the 2-36/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKL MIY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSS STYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS

The 2-36/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 199 is the amino acid sequence defining the 2-36 derivedheavy chain of the 2-36/4-18 antibody 2-36HC-Hole-Cross

QVQLQESGPGLVKPSETLSLTCTVSG GSVSSSNYYWS WIRQPPGKGLE WIG YMYYSGSTKYNPS LKSRVTISVDTSKNQFSLKLSSVTAADTAVYY CAR EVYYYDRSGYYASDGFDIWGQGTMVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSENRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 200 is the amino acid sequence defining the 2-36 derivedlight chain of the 2-36/4-18 antibody 2-36VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLL IY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSP QTFGQGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 201 is the amino acid sequence defining the 4-18 derivedheavy chain of the 2-36/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWV A VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AK DSGYNYGYSW F DPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV LHEALHSHYTQKSLSLSPGK

SEQ ID NO: 202 is the amino acid sequence defining the 4-18 derivedlight chain of the 2-36/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY KDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTY PNWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS

The 2-30/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 203 is the amino acid sequence defining the 2-30 derivedheavy chain of the 2-30/1-68 antibody 2-30HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYTMH WVRQAPGKGLEW VA AISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCAR SILYGGGMDVWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 204 is the amino acid sequence defining the 2-30 derivedlight chain of the 2-30/1-68 antibody 2-30VLCH1

DIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGQAPKLL IY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNSY PLTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 205 is the amino acid sequence defining the 1-68 derivedheavy chain of the 2-30/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEW MGGFDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVY YCAT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 206 is the amino acid sequence defining the 1-68 derivedlight chain of the 2-30/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPK LMIY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYT SSSTYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS

The 2-30/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 207 is the amino acid sequence defining the 2-30 derivedheavy chain of the 2-30/4-18 antibody 2-30HC-Hole-Cross

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYTMH WVRQAPGKGLEW VA AISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCAR SILYGGGMD VWGQGTTVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 208 is the amino acid sequence defining the 2-30 derivedlight chain of the 2-30/4-18 antibody 2-30VLCH1

DIQLTQSPSSLSASVGDRVTITC RASQGISSYLA WYQQKPGQAPKLL IY AASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQLNSY PL TFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 209 is the amino acid sequence defining the 4-18 derivedheavy chain of the 2-30/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEW VA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCAK DSGYNYGYSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 210 is the amino acid sequence defining the 4-18 derivedlight chain of the 2-30/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVI Y KDSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSG TYPNWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS

The 2-7/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 211 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/4-8(39/51) antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKAL EWLA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTAT YYCAH HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 212 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/4-8(39/51) antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPK LMIY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYT TSSTVFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 213 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 2-7/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEW MG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY YCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 214 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 2-7/4-8(39/51) antibody 4-8LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVI Y QDNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSST AVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSH RSYSCQVTHEGSTVEKTVAPTECS

The 1-57/1-87 bispecific antibody sequence can comprise:

SEQ ID NO: 215 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/1-87 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEW VG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTA VYYCAR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIF PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 216 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/1-87 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRL LIY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGS SPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC

SEQ ID NO: 217 is the amino acid sequence defining the 1-87 derivedheavy chain of the 1-57/1-87 antibody 1-87HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEW MG G F DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVY YCAT GIAVIGPPPSTYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 218 is the amino acid sequence defining the 1-87 derivedlight chain of the 1-57/1-87 antibody 1-87LC

QSALTQPASVSGSPGQSITISCTGTS SDVGGYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 1-57/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 219 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/4-8(39/51) antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 220 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/4-8(39/51) antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 221 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 1-57/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 222 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 1-57/4-8(39/51) antibody 4-8LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 2-7/2-51 bispecific antibody sequence can comprise:

SEQ ID NO: 223 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/2-51 antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG F SLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 224 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/2-51 antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSST VFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSC

SEQ ID NO: 225 is the amino acid sequence defining the 2-51 derivedheavy chain of the 2-7/2-51 antibody 2-51 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAYKSTWYFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 226 is the amino acid sequence defining the 2-51 derivedlight chain of the 2-7/2-51 antibody 2-51LC

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRM GFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS

The 2-15/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 227 is the amino acid sequence defining the 2-15 derivedheavy chain of the 2-15/4-8(39/51) antibody 2-15HC-Hole-Cross

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDIWGQGTMITVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSC SVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 228 is the amino acid sequence defining the 2-15 derivedlight chain of the 2-15/4-8(39/51) antibody 2-15VLCH1

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADCYC SSYTSSST FVFGTGTKVTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSC

SEQ ID NO: 229 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 2-15/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG RNIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQTVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 230 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 2-15/4-8(39/51) antibody 4-8LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY Q DNKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 1-57/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 231 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/4-18 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG RTRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYC AR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 232 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/4-18 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLI Y GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPSTFGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 233 is the amino acid sequence defining the 4-18 derivedheavy chain of the 1-57/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG FTFSSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 234 is the amino acid sequence defining the 4-18 derivedlight chain of the 1-57/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAK Q YAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC Q STDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-7/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 235 is the amino acid sequence defining the 2-7 derived heavychain of the 2-7/1-68 antibody 2-7HC-Hole-Cross

QITLKESGPTLVKPTQTLTLTCTFSG FSLSTSGVGVG WIRQPPGKALEW LA LIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCA H HKIERIFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSH YTQKSLSLSPGK

SEQ ID NO: 236 is the amino acid sequence defining the 2-7 derived lightchain of the 2-7/1-68 antibody 2-7VLCH1

QSALAQPASVSGSPGQSITISC TGTSSDVGAYNYVS WYQQHPGKAPKLMVSNRFSGSKSGNTASLTISGLQAEIY DVSKRPS GDEADYYC SSYTTSST VFGGGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSC

SEQ ID NO: 237 is the amino acid sequence defining the 1-68 derivedheavy chain of the 2-7/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWMG GEDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHE ALHSHYTQKSLSLSPGK

SEQ ID NO: 238 is the amino acid sequence defining the 1-68 derivedlight chain of the 2-7/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLM IY EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSST YVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 4-20/4-18 bispecific antibody sequence can comprise:

SEQ ID NO: 239 is the amino acid sequence defining the 4-20 derivedheavy chain of the 4-20/4-18 antibody 4-20HC-Hole-Cross

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHS HYTQKSLSLSPGK

SEQ ID NO: 240 is the amino acid sequence defining the 4-20 derivedlight chain of the 4-20/4-18 antibody 4-20VLCH1

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVTFGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSC

SEQ ID NO: 241 is the amino acid sequence defining the 4-18 derivedheavy chain of the 4-20/4-18 antibody 4-18HC-Knob

QVQLVESGGGVVQPGRSLRLSCAASG F T F SSYGMH WVRQAPGKGLEWVA VISYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK DSGYNYGYSWEDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHY TQKSLSLSPGK

SEQ ID NO: 242 is the amino acid sequence defining the 4-18 derivedlight chain of the 4-20/4-18 antibody 4-18LC

SYELTQPPSVSVSPGQTARITC SADALAKQYAY WYQQKPGQAPVLVIY K DSERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC QSTDNSGTYPN WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYS CQVTHEGSTVEKTVAPTECS

The 2-15mut/2-51 bispecific antibody sequence can comprise:

SEQ ID NO: 243 is the amino acid sequence defining the 2-15mut derivedheavy chain of the 2-15mut/2-51 antibody 2-15HC-Hole-Cross

QVQLVQSGAEVKKPGASVRVSCKASG YTFTGYYMH WVRQAPGQGLEWMG WINPISDGTNYAQKFQGWVTMTRDTSISTVYMELSRLRSDDTAVYYCAR GGSRCSGGNCYGWAYDAFDIWGQGTMITVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSC SVLHEALHSHYTQKSLSLSPGK

SEQ ID NO: 244 is the amino acid sequence defining the 2-15mut derivedLight chain of the 2-15mut/2-51 antibody 2-15mutVLCH1

QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLM IY DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADSYC SSYTSSST FVFGTGTKVTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSC

SEQ ID NO: 245 is the amino acid sequence defining the 2-51 derivedheavy chain of the 2-15mut/2-51 antibody 2-51 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G F DPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GWAYKSTWYFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYT QKSLSLSPGK

SEQ ID NO: 246 is the amino acid sequence defining the 2-51 derivedlight chain of the 2-15mut/2-51 antibody 2-51LC

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLM IY EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRM GFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS

The 4-20/4-8(39/51) bispecific antibody sequence can comprise:

SEQ ID NO: 247 is the amino acid sequence defining the 4-20 derivedheavy chain of the 4-20/4-8(39/51) antibody 4-20HC-Hole-Cross

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG IINPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PGGGSYQEFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHS HYTQKSLSLSPGK

SEQ ID NO: 248 is the amino acid sequence defining the 4-20 derivedlight chain of the 4-20/4-8(39/51) antibody 4-20VLCH1

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS A ASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVT FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSC

SEQ ID NO: 249 is the amino acid sequence defining the 4-8(39/51)derived heavy chain of the 4-20/4-8(39/51) antibody 4-8(39/51) HC-Knob

QVQLVQSGAEVKKAGSSVKVSCKASG GTFSSHTIT WVRLAPGQGLEWMG R NIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAS LQ TVDTAIEKYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLS LSPGK

SEQ ID NO: 250 is the amino acid sequence defining the 4-8(39/51)derived light chain of the 4-20/4-8(39/51) antibody 4-8LC

SYELTQPPSVSVSPGQTASITC SGDKLGDKYAC WYQQKPGQSPVLVIY QD NKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYC QAWDSSTAV FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS TVEKTVAPTECS

The 1-57/2-51 bispecific antibody sequence can comprise:

SEQ ID NO: 251 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/2-51 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG R TRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYCAR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 252 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/2-51 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPST FGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSC

SEQ ID NO: 253 is the amino acid sequence defining the 2-51 derivedheavy chain of the 1-57/2-51 antibody 2-51 HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G FDPEDVETIYAQQFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GW AYKSTWYFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPG K

SEQ ID NO: 254 is the amino acid sequence defining the 2-51 derivedlight chain of the 1-57/2-51 antibody 2-51LC

QSALTQPPSASGSPGQSVTISC TGTSSDVGGYNYVS WYQQHPGKAPKLMI Y EVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYC SSYAGSRMG FGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTH EGSTVEKTVAPTECS

The 4-20/1-87 bispecific antibody sequence can comprise:

SEQ ID NO: 255 is the amino acid sequence defining the 4-20 derivedheavy chain of the 4-20/1-87 antibody 4-20HC-Hole-Cross

QVQLLQSGAEVKKPGASVKVSCKASG YSFTSYYMH WVRQAPGQGLEWMG I INPSGGGTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR PG GGSYQEFDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSL SPGK

SEQ ID NO: 256 is the amino acid sequence defining the 4-20 derivedlight chain of the 4-20/1-87 antibody 4-20VLCH1

DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIS A ASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYNTLQVT FGGGTKVEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSC

SEQ ID NO: 257 is amino acid sequence defining the 1-87 derived heavychain of the 4-20/1-87 antibody 1-87HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKGLEWMG G FDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GI AVIGPPPSTYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQK SLSLSPGK

SEQ ID NO: 258 is the amino acid sequence defining the 1-87 derivedlight chain of the 4-20/1-87 antibody 1-87LC

QSALTQPASVSGSPGQSITISCTGTS SDVGGYNYVS WYQQHPGKAPKLMI Y DVSKRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

The 1-57/1-68 bispecific antibody sequence can comprise:

SEQ ID NO: 259 is the amino acid sequence defining the 1-57 derivedheavy chain of the 1-57/1-68 antibody 1-57HC-Hole-Cross

EVHLVESGGGLVQPGGSLRLSCAASG FTFSDHYMD WVRQAPGKGLEWVG R TRNKANSYTTEYAASVKGRFTISRDDAKNSLYLQMNSLKTEDTAVYYCAR VHRWAYCINGVCFGAYSDYWGQGTLVTVSSASTAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVLHEALH SHYTQKSLSLSPGK

SEQ ID NO: 260 is the amino acid sequence defining the 1-57 derivedlight chain of the 1-57/1-68 antibody 1-57VLCH1

EIVLTQSPGTLSLSPGERATLSC RASQSVSSSYLA WYQQKPGQAPRLLIY GASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPST FGQGTKLEIKSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSC

SEQ ID NO: 261 is the amino acid sequence defining the 1-68 derivedheavy chain of the 1-57/1-68 antibody 1-68HC-Knob

QVQLVQSGAEVKKPGASVKVSCKVSG YTLIELSMH WVRQAPGKG LEWMGG FDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT GW AVAGSSDVWYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQK SLSLSPGK

SEQ ID NO: 262 is the amino acid sequence defining the 1-68 derivedlight chain of the 1-57/1-68 antibody 1-68LC

QSALTQPPSVSGSPGQSVTISC TGTSSDVGSYNRVS WYQQPPGTAPKLMI Y EVSNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS

In some embodiments, a bispecific antibody can be generated from anycombination of two monoclonal antibodies described herein. In someembodiments, the subject matter disclosed herein related to the DNAsequence encoding a bispecific antibody comprising any SEQ ID NO from1-262 or a combination of SEQ ID NOs 1-262. In some embodiments, thesubject matter disclosed herein related to the RNA sequence encoding abispecific antibody comprising any SEQ ID NO from 1-262 or a combinationof SEQ ID NOs 1-262.

EXAMPLES

Examples are provided below to facilitate a more complete understandingof the invention. The following examples illustrate the exemplary modesof making and practicing the invention. However, the scope of theinvention is not limited to specific embodiments disclosed in theseExamples, which are for purposes of illustration only, since alternativemethods can be utilized to obtain similar results.

Examples for Monoclonal Antibodies Example 1—Patient Antibody Response

By studying 40 COVID-19 patient cases in great detail, it was found thatpatients with more severe disease develop more robust antibodies intheir blood to the coronavirus. These antibodies include antibodiesspecific to the spike protein trimer. For the disease to be classifiedas severe, the COVID-19 patients need mechanical ventilation in anintensive care unit and treatment with hydroxychloroquine, remdesivir,and/or tocilizumab. For the disease to be classified as non-severe, theCOVID-19 patients do not require intensive care. FIGS. 2A-G show ELISAbinding data in which various COVID-19 patient plasma samples, indicatedby different colored lines, were tested for their ability to bind toSARS-CoV-2 nucleocapsid antigen (FIGS. 2A and D), SARS-CoV-2 envelopetrimer antigen (FIGS. 2B and E), or SARS-CoV envelope trimer antigen(FIGS. 2C and F). This binding assay is used to determine whether theplasma samples contain an element, most likely antibodies, that caninteract with SARS-CoV-2 and SARS-CoV antigens, suggesting an immuneresponse to the antigens. Those plasma samples that interact with bothSARS-CoV-2 and SARS-CoV antigens indicate potential for utilizing thesamples in neutralization of the antigens and the antigen carryingviruses. FIG. 2G shows a plot of the data from FIGS. 2A-F, whichillustrates that higher SARS-CoV-2 antibody responses are present inplasma samples of patients with severe COVID-19 as compared to thosepatients with non-severe COVID-19.

Example 2—Antibody Responses Correlated Potencies in NeutralizingSARS-CoV-2

FIGS. 3A-J shows that stronger binding antibody responses correlate wellwith greater potencies in neutralizing SARS-CoV-2. Neutralization assaysin which various COVID-19 patient plasma samples, indicated by differentcolored lines, were tested for their ability to protect the target cellsfrom infection by SARS-CoV-2 in a single-cycle pseudovirus infectivityassay (FIGS. 3A and D), by SARS-CoV in a single-cycle pseudovirusinfectivity assay (FIGS. 3B and E), and by SARS-CoV-2 in a replicationcompetent live virus infectivity assay (FIGS. 3C and F). This assay isused to determine whether the plasma samples contain an element, mostlikely antibodies, that can effectively block SARS-CoV-2 or SARS-CoVinfection. FIG. 3G shows plotting the dilution (ID₅₀) from FIGS. 3A-F atwhich the plasma inhibits 50% of virus infection. Higher SARS-CoV-2inhibitory dilutions are present in plasma samples of patients withsevere COVID-19, indicating a potentially more potent antibody responsein these patients. FIGS. 3H-J show that the IC₅₀ values obtained bypseudovirus neutralization assay correlate well with the IC₅₀ valuesobtained from live virus neutralization assay (FIG. 311 ), the dilutionsof plasmas achieving half of the readout of OD₄₅₀ values tested by ELISAin FIG. 2 (FIG. 3I), and with the OD₄₅₀ values of the plasma binding toS trimer when diluted 400-fold in FIG. 2 (FIG. 3J). The data hereindicates that the antibody binding ability to SARS-CoV-2 S trimer inthe COVID-19 plasma samples are well correlated with the neutralizationability, suggesting that the single B cells sorted by SARS-CoV-2 Strimer from COIVD-19 patients should have neutralization ability intheir secreted antibodies.

Example 3—Schematics for Identifying Potent Neutralizing AntibodiesAgainst COVID-19

From the COVID-19 patient cases that indicated the most robust antibodyresponses in the experiments in FIGS. 2 and 3 , blood sample wasobtained and subjected to the experimental schema depicted in FIGS. 4A-Cin order to identify monoclonal antibodies that could powerfullyneutralize the SARS-CoV-2 virus. From each blood sample, theantibody-producing cells known as CD27+ memory B cells were isolated. Inparticular, the subset of cells that could bind the viral spike proteintrimer were isolated.

The experimental protocol can include the following steps. PBMCs frominfected individuals were collected and stained with LIVE/DEAD™ FixableYellow Dead Cell Stain Kit (Invitrogen, cat: L34959) at room temperaturefor 20 minutes to exclude dead cells. Then the cells were incubated with10 μg/ml spike trimer firstly and further an antibody cocktail foridentification of SARS-CoV-2 S trimer specific B cells. The cocktailconsisted of CD3-PE-CF594(BD Biosciences, cat:562406),CD19-PE-cy7(Biolegend, cat:302216), CD20-APC-cy7(Biolegend, cat:302314),IgM-V450(BD Biosciences, cat:561286), CD27-PerCP-Cy5.5(BD Biosciences,cat:560612) and Anti-His-PE (Biolegend, cat:362603). Spikertrimer-specific single B cells were gated as CD3-CD19 CD27+Spike trimer+and sorted into Eppendorf® LoBind microcentrifuge tubes (Sigma, cat:Z666505). After antigen-specific CD27+ memory B cell enrichment, 1310 Bcells were loaded on 10× Chromium Chips. All of the experimentalprocesses were performed before library preparation in a BSL3-levellaboratory. Single-cell lysis and RNA first-strand synthesis wasperformed using 10× Chromium Single Cell 5′ Library & Gel Bead Kitaccording to the manufacturer's protocol. The following RNA and VDJlibrary preparation is performed according to the manufacturer'sprotocol (Chromium Single Cell V(D)J Reagent Kits, 10× Genomics) in aBSL-2 laboratory. Sequencing was performed on a Hiseq 2500 platformrunning Rapid SBS Kit V2 2×100 bp kit (Illumina), with a 26×91 pair-endreading mode. Armed with this information, each monoclonal antibody wasreconstructed, now over 250 monoclonal antibodies are obtained by thismethod.

As shown in FIG. 9 , there is a total of 254 monoclonal antibodies(mAbs) currently synthesized and tested. These include bindingantibodies, pseudovirus neutralizing mAbs, and live virus neutralizingantibodies. The binding antibodies include 121 spike protein trimertargeting mAbs, 38 RBD-targeting mAbs, and 83 non-RBD-targeting mAbs.The pseudovirus neutralizing mAbs include 52 spike proteintrimer-targeting mAbs, 28 RBD-targeting mAbs, and 24 non-RBD-targetingmAbs. The live virus neutralizing antibodies include 32 spike proteintargeting mAbs, 13 RBD-targeting mAbs, and 19 non-RBD-targeting mAbs.217 mAbs were tested for live virus neutralization.

Example 4

FIGS. 5A-D show characterization of the initially identified sixmonoclonal antibodies that were synthesized and purified, including thehigh binding ability to the SARS-CoV-2 S trimer (FIG. 5A) and to thevirus receptor binding domain (FIG. 5B), and the neutralization capacityof the virus with high potency in both pseudovirus (FIG. 5C) and livereplication competent virus (FIG. 5D) assays. Each colored lineindicates a different monoclonal antibody. The half maximal effectiveconcentration (EC₅₀) tested by ELISA and the half maximal inhibitoryconcentration (IC₅₀) tested by neutralization assay are presented to theside of each antibody. SARS-CoV antibody CR3022 is a control which canbind to but not neutralize SARS-CoV-2. These six antibodies are specificto SARS-CoV-2 S trimer, and three of them are RBD binders and threenon-RBD binders. All of these six antibodies have neutralizationactivity against SARS-CoV-2 pseudovirus and live viruses and 2-15 is themost potent one. The binding data showed that these antibodies could bedivided into at least two groups with different mechanisms inneutralizing the virus.

In order to determine where on the SAR-CoV-2 envelope these monoclonalantibodies bind, competition ELISA experiments were performed in orderto map the epitopes of these new monoclonal antibodies. As shows inFIGS. 6A-F, each antibody was biotinylated, mixed with other serialdiluted antibodies and then incubated with the spike protein (S) trimer.The binding of biotinylated antibodies to S trimer with the presence ofother monoclonal antibodies was detected by ELISA. Each colored linerepresents a different monoclonal antibody. Six of the characterizedmonoclonal antibodies are categorized into two classes: RBD binding(FIGS. 6A-C) and non-RBD binding (FIGS. 6D-F). There is no competitionbetween the two classes of antibodies but within the two classes,providing the possibility for combination of RBD and non-RBD bindersagainst COVID-19 because they have different mechanisms of neutralizingthe virus.

Example 5

To further characterize the binding affinity of these new monoclonalantibodies, surface plasmon resonance experiments were performed todetermine the binding affinity of the most promising monoclonalantibodies to the SARS-CoV-2 spike trimer. As shown in FIGS. 7A-E, eachpanel represents the binding affinity and binding kinetics of theindicated monoclonal antibody (i.e., 2-4, 2-15, 2-38, etc.) to theSARS-CoV-2 spike timer. The lower KD1 value indicates a higher antibodybinding affinity. Colored lines indicate different dilutions of therespective antibody tested.

Example 6

FIGS. 8A-D show initial screenings of mAbs that bind and neutralize theSARS-CoV-2 virus. FIG. 8A shows mAbs binding to spike trimer protein.FIG. 8B shows mAbs binding to the receptor-binding domain (RBD). FIG. 8Cshows IC₅₀ values for pseudotyped virus infection. FIG. 8D shows percentinhibition values for live virus infection. FIG. 9 shows summary ofsynthesized antibodies.

Example 7

As shown in FIGS. 10A-I, the potent neutralizing mAbs disclosed hereincan bind to the receptor binding domain of the spike protein trimer, tothe N-terminal domain of the spike protein trimer or to a differentepitope on the spike protein trimer. Each colored line shown in FIGS.10A-I indicates a different monoclonal antibody utilized in an ELISAbinding assay. FIGS. 10A, D, and G show binding to spike protein trimer.FIGS. 10B, E, and H show binding to the RBD. FIGS. 10C, F, and I showbinding to the NTD. FIGS. show binding of mAbs, which potently bind theRBD. FIGS. 10D-F show binding of mAbs, which potently bind the NTD.FIGS. 10G-I show binding of mAb, which bind epitopes other than the RBDor the NTD. Monoclonal antibodies 2-15, 2-7, 1-57, 2-4, 2-38, 1-20,2-30, and 4-20 specifically target the RBD of the spike protein trimer.They show no binding affinity for the NTD of the spike protein trimer asshown in FIG. 10C. Monoclonal antibodies 4-18, 5-24, 5-7, and 1-68specifically target the NTD of the spike protein trimer. Theseantibodies show no binding affinity for the RBD of the spike proteintrimer as shown in FIG. 10E. Monoclonal antibodies 2-43, 4-8, 4-19,2-51, and 2-17 target at least one other epitope on the spike proteintrimer. These antibodies do not show binding affinity for the RBD norfor the NTD as shown in FIGS. 1011 and I, respectively.

Example 8

FIGS. 11A-F show SARS-CoV-2 neutralization activity of select mAbs. FIG.11A shows neutralization activity of RBD-targeting mAbs neutralizing apseudovirus infection. The range of IC₅₀ concentrations for theseantibodies is from 0.005 μg/ml to 0.512 μg/ml. FIG. 11B showsneutralization activity of NTD-targeting mAbs neutralizing a pseudovirusinfection. The range of IC₅₀ concentrations for these antibodies is from0.013 μg/ml to 0.767 μg/ml. FIG. 11C shows neutralization activity ofmAbs, which target epitopes other than the RBD or the NTD, neutralizinga pseudovirus infection. The range of IC₅₀ concentrations for theseantibodies is from 0.070 μg/ml to 0.652 μg/ml. FIG. 11D showsneutralization activity of RBD-targeting mAbs neutralizing a live virusinfection. The range of IC₅₀ concentrations for these antibodies is from0.001 μg/ml to 0.103 μg/ml. FIG. 11E shows neutralization activity ofNTD-targeting mAbs neutralizing a live virus infection. The range ofIC₅₀ concentrations for these antibodies is from 0.011 μg/ml to 0.034μg/ml. FIG. 11F shows neutralization activity of mAbs, which targetepitopes other than the RBD or the NTD, neutralizing a live virusinfection. The range of IC₅₀ concentrations for these antibodies is from0.003 μg/ml to 0.079 μg/ml.

Example 9

FIGS. 12A-B show a CryoEM structure of an RBD-targeting monoclonalantibody. FIG. 12A shows a side view of the structure while FIG. 12Bshows a top view of the structure. The mAb is shown in blue ribbondirectly adjacent to the RBD, which is shown in green ribbon. The CryoEMstructure suggests that the mAb targeting the RBD does not directlyinteract with the NTD, which is shown in brown ribbon.

FIGS. 13A-B show a CryoEM structure of an NTD-targeting monoclonalantibody. FIG. 13A shows a side view of the structure while FIG. 13Bshows a top view of the structure. The mAb is shown in blue ribbondirectly adjacent to the NTD, which is shown in brown ribbon. The CryoEMstructure suggests that the mAb targeting the NTD does not directlyinteract with the RBD, which is shown in green ribbon.

FIG. 14 shows three SARS-CoV-2 neutralizing epitope clusters identifiedon the spike protein trimer. The NTD cluster is shown in blue ribbon.The RBD is shown in green ribbon. Other color indicate potentialneutralizing epitopes on the spike protein, which are different from theNTD and RBD clusters.

Example 10—Potent Neutralizing Monoclonal Antibodies Directed toMultiple Epitopes on the SARS-CoV-2 Spike

Abstract

The SARS-CoV-2 pandemic rages on with devasting consequences on humanlives and the global economy. The discovery and development ofvirus-neutralizing monoclonal antibodies could be one approach to treator prevent infection by this novel coronavirus. Here we report theisolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5infected patients hospitalized with severe disease. Among these are 19antibodies that potently neutralized the authentic SARS-CoV-2 in vitro,9 of which exhibited exquisite potency, with 50% virus-inhibitoryconcentrations of 1 to 9 ng/mL. Epitope mapping showed this collectionof 19 antibodies to be about equally divided between those directed tothe receptor-binding domain (RBD) and those to the N-terminal domain(NTD), indicating that both of these regions at the top of the viralspike are quite immunogenic. In addition, two other powerfulneutralizing antibodies recognized quaternary epitopes that areoverlapping with the domains at the top of the spike. Cryo-electronmicroscopy structures of one antibody targeting RBD, a second targetingNTD, and a third bridging RBD and NTD revealed recognition of theclosed, “all RBD-down” conformation of the spike. Several of thesemonoclonal antibodies are promising candidates for clinical developmentas potential therapeutic and/or prophylactic agents against SARS-CoV-2.

Background

A novel coronavirus, now termed SARS-CoV-2^(1,2), has caused nearly 8million confirmed infections globally, leading to about 450,000 deaths.This pandemic has also put much of the world on pause, withunprecedented disruption of lives and unparalleled damage to theeconomy. A return to some semblance of normalcy will depend on scienceto deliver an effective solution, and the scientific community hasresponded admirably. Drug development is well underway, and vaccinecandidates are entering clinical trials. Another promising approach isthe isolation of SARS-CoV-2-neutralizing monoclonal antibodies (mAbs)that could be used as therapeutic or prophylactic agents. The primarytarget for such antibodies is the viral spike, a trimeric protein 3,4that is responsible for binding to the ACE2 receptor on the hostcell^(1,3,5,6). The spike protein is comprised of two subunits. The S1subunit has two major structural elements: RBD and NTD; the S2 subunitmediates virus-cell membrane fusion after the RBD engages ACE2. Reportsof discovery of neutralizing mAbs that target the RBD have beenpublished recently⁷⁻¹¹. We now describe our efforts in isolating andcharacterizing a collection of mAbs that not only target multipleepitopes on the viral spike but also show exquisite potency inneutralizing SARS-CoV-2.

Patient Selection

Forty patients with PCR-confirmed SARS-CoV-2 infection were enrolled inan observational cohort study on virus-neutralizing antibodies. Plasmasamples from all subjects were first tested for neutralizing activityagainst SARS-CoV-2 pseudovirus (Wuhan-Hu-1 spike pseudotyped withvesicular stomatitis virus). Widely varying neutralizing titers wereobserved, with IC₅₀ ranging from a reciprocal plasma dilution of <100 to˜13,000 (FIG. 15A). Five patients were chosen for mAb isolation becausetheir plasma virus-neutralizing titers were among the highest. Theclinical characteristics of these 5 cases are summarized in FIG. 19 . Inbrief, all were severely ill with acute respiratory distress syndromerequiring mechanical ventilation. Their ages ranged from 50 to 71. Twowere Hispanic females, two were white males, and one was a black male.One patient died, while the others recovered. Importantly, blood forisolation of SARS-CoV-2 mAbs was obtained on day 18 to 32 post onset ofsymptoms.

Monoclonal Antibody Isolation and Construction

Peripheral blood mononuclear cells from each patient were put through anexperimental schema (FIG. 22A) starting with cell sorting by flowcytometry. The sorting strategy focused on live memory B lymphocytesthat were CD3-negative, CD19-positive, and CD27-positive (FIG. 22B). Thefinal step focused on those cells that bound the SARS-CoV-2 spike trimer(S trimer) 4. S trimer-positive memory B cells were enriched (0.4% to1.4%) in the 5 patients as compared to a normal health donor (0.2%)(FIG. 22C). A total of 602, 325, 14, 147, and 145 such B cells fromPatient 1, Patient 2, Patient 3, Patient 4, and Patient 5, respectively,were labelled with a unique hashtag. The cells were then placed into the10× Chromium (10× Genomics) for single-cell 5′ mRNA and V(D)J sequencingto obtain paired heavy (H) and light (L) chain sequences. A carefulbioinformatic analysis was carried out on 1,145 paired sequences todownselect “high-confidence” antigen-specific mAbs. A total of 331 mAbsequences were recovered, representing 252 individual clones. Only 6mAbs were from Patient 3, whereas 44 to 100 mAbs were identified fromeach of the other patients (FIG. 20 ). The VH and VL sequences of 252antibodies (one per clone) were codon-optimized and synthesized, andeach VH and VL gene was then cloned into an expression plasmid withcorresponding constant region of H chain and L chain of human IgG1, andmAbs were expressed by co-transfection of paired full-length H chain andL chain genes into Expi293 cells. The supernatant from eachtransfectionwas collected for the screening assays and antibody purification.

Monoclonal Antibody Screening

All 252 transfection supernatants were screened for binding to S trimerand RBD by enzyme-linked immunosorbent assays (ELISAs), as well as forneutralization against SARS-CoV-2 pseudovirus and live virus. Theseresults are graphically represented in FIGS. and tabulated in FIG. 20 .It was evident that a substantial percentage of the mAbs in thesupernatants bound S trimer, and a subset of those bound RBD.Specifically, 121 supernatants were scored as positive for S trimerbinding, yielding an overall hit rate of 48%. Of these, 38 were positivefor RBD binding while the remaining 83 were negative. It is interestingto note that none of the 13 trimer-specific mAbs from Patient 5recognized RBD. In the pseudovirus neutralization screen, 61supernatants were scored as positive, indicating that half of thetrimer-specific mAbs were virus neutralizing. In particular, 15supernatants retained neutralizing activity even when diluted by1,000-fold or more. In the screen for neutralization against SARS-CoV-2(strain USA-WA1/2020), 41 supernatants were scored as positive,including 10 that neutralized the virus completely (+++). Overall, thisscreening strategy was quite effective in picking up neutralizing mAbs(vertical lines and labelled antibodies at the bottom of FIG. 15B) thatwere later identified as potent.

Sequence Analysis of S Trimer-Specific Monoclonal Antibodies

Of the 121 mAbs that bound S trimer, 88% were IgG isotype, with IgG1being predominant (FIGS. 23A-D). Small numbers of antibodies of IgM andIgA isotypes were also found. Comparison to the IgG repertoire of threehealthy human donors¹², a statistically significant over-representationof IGHV3-30, IGKV3-20, and IGHJ6 genes was observed for this collectionof SARS-CoV-2 mAbs (FIG. 23E). A longer CDRH3 length was also noted(FIG. 23F). Interestingly, the average percentages of somatichypermutation in VH and VL were 2.1 and 2.5, respectively, which weresignificantly lower than those found in healthy individuals (FIG. 23G)and remarkably close to germline sequences.

Antigen Binding and Virus Neutralization

Since the screening for pseudovirus neutralization was performedquantitatively with serial dilutions of the transfection supernatants,we plotted in FIG. 24 the best-fit neutralization curves for 130 samplesthat were positive in at least one of the screens shown in FIG. 15B.Most were non-neutralizing or weakly neutralizing, but 18 showedevidently better potency. One additional supernatant was initiallymissed in the pseudovirus screen (Patient 1 in FIG. 24 ) but was laterfound to be a potent neutralizing mAb. Together, these 19 mAbs werepurified from transfection supernatants and further characterized fortheir binding and neutralization properties. As shown in FIGS. 16A, D,and G, all but one (2-43) of the mAbs bound the S trimer by aquantitative ELISA. Using two other quantitative ELISAs, nine of theantibodies clearly bound RBD (FIGS. 16B, E, and H), with little or nobinding to NTD (FIGS. 16C, F, and I). Eight antibodies bound NTD tovarying degrees, with no binding to RBD. Two mAbs bound neither RBD norNTD, and were therefore categorized as “Others”.

The pseudovirus neutralization profiles for these purified 19 mAbs areshown in the top portion of FIGS. 16J-L. The RBD-directed antibodiesneutralized the pseudovirus with IC₅₀ of 0.005 to 0.512 μg/mL; theNTD-directed antibodies were slightly less potent, with IC₅₀ rangingfrom 0.013 to 0.767 μg/mL. A common feature of the NTD mAbs was theplateauing of virus neutralization at levels short of 100%. Twoantibodies, categorized as “Others”, neutralized with IC₅₀ of 0.071 and0.652 μg/mL, with mAb 2-51 exhibiting the plateauing effect typical ofNTD antibodies. Antibody neutralization of the authentic or liveSARS-CoV-2 (strain USA-WA1/2020) was carried out using Vero cellsinoculated with a multiplicity of infection of 0.1. As shown in thebottom portion of FIGS. 16M-O, the RBD-directed antibodies againneutralized the virus but with IC₅₀ of 0.0007 to 0.209 μg/mL; theNTD-directed antibodies showed similar potency, with IC₅₀ ranging from0.007 to 0.109 μg/mL. Here, the plateauing effect seen in thepseudovirus neutralization assay was less apparent. Antibodies 2-43 and2-51 neutralized the live virus with IC₅₀ of 0.003 and 0.007 μg/mL,respectively. Overall, nine mAbs exhibited exquisite potency inneutralizing authentic SARS-CoV-2 in vitro with IC₅₀ of 0.009 μg/mL orless, including four directed to RBD (2-15, 2-7, 1-57, and 1-20), threeto NTD (2-17, 5-24, and 4-8), and two to undetermined regions on the Strimer (2-43 and 2-51). It is remarkable that Patient 2 alonecontributed five of the top nine SARS-CoV-2 neutralizing mAbs.

Epitope Mapping

All 19 potent neutralizing mAbs (FIG. 16 ) were further studied inantibody competition experiments to gain insight into their epitopes. Inaddition, 12 mAbs that bound the S trimer strongly during the initialsupernatant screen were also chosen, including 5 that bound RBD (1-97,2-26, 4-13, 4-24, and 4-29) and 7 that did not bind RBD (1-21, 2-29,4-15, 4-32, 4-33, 4-41, and 5-45). Four of these mAbs were weak inneutralizing SARS-CoV-2 pseudovirus, and the remaining 8 werenon-neutralizing (FIG. 25 ). First, a total of 16 non-RBD mAbs wereevaluated for competition in binding to S trimer by ELISA in a“checkerboard” experiment. The extent of the antibody competition isreflected by the intensity of the heatmap shown in FIG. 17A. There isone large cluster (A) of mAbs that competed with one another, and itpartially overlaps a small cluster (B). A third cluster (C) does notoverlap at all. Note that all but one of the antibodies in cluster Arecognized NTD. Antibody 2-51 is clearly directed to the NTD region eventhough it could not bind NTD. Moreover, one mAb each from clusters B andC also recognized NTD, thereby indicating that all three clusters arewithin or near the NTD. One mAb, 1-21, appears to have a uniquenon-overlapping epitope (epitope region D).

Second, a similar “checkerboard” competition experiment was carried outby ELISA for 14 of our RBD-directed mAbs plus CR3022^(13,14). Here, theheatmap shows that there are four epitope clusters that are seriallyoverlapping (FIG. 17B). In FIGS. 17C-D. There is one large cluster (E)that contains mAbs largely capable of blocking ACE2 binding.Furthermore, 4 antibodies in this cluster lost binding to a mutant RBD(L455R, A475R, G502R) that could no longer bind ACE2 (our unpublishedfindings). Taken together, these results suggest that most of the mAbsin cluster E are directed to the ACE2-binding interface of RBD. The nextcluster (F) connects to both cluster E and cluster G, the location ofwhich is defined by its member CR3022¹⁵. Lastly, cluster G overlapsanother cluster (H), which includes 1-97 that strongly inhibited thebinding of 2-30 to the S trimer. This finding suggests that cluster Hmay be proximal to one edge of cluster E.

One potent neutralizing mAb, 2-43, did not bind S trimer by ELISA (FIG.16 ) and thus could not be tested in the above competition experiments.However, 2-43 did strongly bind S trimer when expressed on the cellsurface as determined by flow cytometry, and this binding was competedout by itself but not by RBD, NTD, ACE2, or the soluble S trimer4 (FIGS.26A-C). NTD-directed mAbs had only a modest effect on its binding tocell-surface S trimer, but numerous RBD-directed mAbs in cluster Epotently blocked the binding of 2-43, demonstrating that this antibodyis likely targeting a quaternary epitope on the top of RBD that includesa portion of the interface with ACE2.

The results in FIGS. 17A-B and FIGS. 26A-C could be represented by twosets of Venn diagrams shown in FIGS. 17C-D. In the non-RBD region, thepotent neutralizing mAbs reside exclusively in cluster A and bind apatch on the NTD. Weaker neutralizing mAbs recognize a region at theinterface between clusters A and B. In the RBD region, the most potentneutralizing mAbs also group together within one cluster (E). Given thatall block ACE2 binding, it is likely they recognize the top of RBD andneutralize the virus by competitive inhibition of receptor binding.Cluster G contains CR3022, a mAb known to be directed to an epitope on acryptic site on the side of RBD when it is in the “up” position¹⁵.Cluster F is therefore likely situated between the top and this“cryptic” site. The Venn diagram also suggests that cluster H may occupya different side surface near the top of RBD, perhaps in the regionrecognized by S3098.

Cryo-Electron Microscopy

To further understand antibody recognition of the viral spike and to aidthe interpretation of the mapping studies, we determined cryo-EMstructures of Fabs from three mAbs in complex with the S trimer4. First,single-particle analysis of the complex with 2-4 Fab (RBD-directed)yielded maps of high quality (FIG. 18 a ; FIG. 21 ; FIGS. 27A-F), withthe most abundant particle class representing a 3-Fab-per-trimercomplex, refined to an overall resolution of 3.2 Å. While density forthe constant portion of the Fabs was visible, it was blurred due tomolecular motion, and thus only the variable domains were included inthe molecular model. Fab of 2-4 bound the spike protein near the apex,with all RBDs in the “down” orientation, and the structure of theantibody-bound spike protein was highly similar to previously publishedunliganded spike structures in the “all-down” conformation3,4. The 2-4epitope on RBD has a buried surface area of 751 A2, sharing 284 A2 withthe interface of ACE2. Detailed interactions between 2-4 and RBD, alongwith comparative analyses, are discussed and exhibited in FIG. 28 .Overall, FIG. 18A shows that neutralization of SARS-CoV-2 by mAb 2-4likely results from locking RBD in the down conformation while alsooccluding access to ACE2.

Second, we also produced 3D cryo-EM reconstructions of the Fab of 4-8(NTD-directed) in complex with the S trimer (FIG. 21 ; FIG. 29 ). Twomain particle classes were observed—one for a 3-Fab-bound complex withall RBDs “down” at 3.9 Å resolution (FIG. 18B), and another a3-Fab-bound complex with one RBD “up” at 4.0 Å resolution (FIG. 30 ).However, molecular motion prevented visualization of the interaction athigh resolution. Nevertheless, the density in the 4-8 map reveals theoverall positions of the antibody chains targeting NTD, and helps toanchor the results of the antibody competition experiments. How suchbinding to the tip of NTD results in SARS-CoV-2 neutralization remainsunclear.

Third, a 7.8 Å resolution reconstructions of the Fab of 2-43 in complexwith the S trimer (FIG. 21 ; FIG. 3I) revealed three bound Fabs, eachtargeting a quaternary epitope on the top of the spike that included theRBD of one protomer and the NTD of another (FIG. 4C), consistent withthe epitope mapping results (FIG. 26 and FIG. 17B). Given thesefindings, the inability of 2-43 to bind S trimer by ELISA is likely anartifact of the assay format, as this mAb did bind the spike expressedon the cell surface and in the cryo-EM study. FIG. 18C suggests that2-43 could block SARS-CoV-2 infection by occluding the site necessaryfor ACE2 binding.

Armed with these three cryo-EM reconstructions, we used the Venndiagrams from FIG. 17B to map the epitopes of many of our SARS-CoV-2neutralizing mAbs onto the surface of the spike (FIG. 18D). This isobviously a rough approximation since antibody footprints are muchlarger than the area occupied by the mAb number. However, the spatialrelationship of the antibody epitopes should be reasonably representedby FIG. 18D.

DISCUSSION

We have discovered a collection of SARS-CoV-2-neutralizing mAbs that arenot only potent but also diverse. Nine of these antibodies canneutralize the authentic virus in vitro at concentrations of 9 ng/mL ofless (FIG. 16B), including 4 directed to RBD, 3 directed to NTD, and 2to quaternary epitopes nearby. Surprisingly, many of the these mAbs haveV(D)J sequences close to germline sequences, without extensive somatichypermutations (FIG. 23E), a finding that bodes well for vaccinedevelopment. Our most potent RBD-specific mAbs (e.g., 2-15, 2-7, 1-57,and 1-20) compare favorably with such antibodies recentlyreported^(7,8,10,16-20) including those with high potency^(9,11,21,22).It appears from the epitope mapping studies that mAbs directed to thetop of RBD strongly compete with ACE2 binding and potently neutralizethe virus, whereas those directed to the side surfaces of RBD do notcompete with ACE2 and neutralize less potently (FIGS. 3B and 4D). Ourcollection of non-RBD neutralizing mAbs is unprecedented in that suchantibodies only have been sporadically reported and only withsubstantially lower potencies 22-24. The most potent of these mAbs aredirected to (e.g., 2-17, 5-24, and 4-8) or overlapping with (2-51) apatch on the NTD (FIGS. 3B and 4D). It is unclear how NTD-directed mAbsblock SARS-CoV-2 infection and why their neutralization profiles aredifferent from those of RBD-directed antibodies (FIG. 16B).Nevertheless, vaccine strategies that do not include NTD will be unableto induce an important class of virus-neutralizing antibodies.

The isolation of two mAbs (2-43 and 2-51) directed to epitopes that donot map to RBD and NTD is also unprecedented. Cryo-EM of 2-43 bound tothe S trimer has confirmed its epitope as quaternary in nature, crossingfrom the top of RBD to the top of an adjacent NTD (FIG. 18C). It will beequally informative to understand the epitope of 2-51 as well. In thisstudy, we also show the first evidence by cryo-EM for a neutralizing mAb(4-8) bound to the NTD of the viral spike (FIG. 18B), as well as anotherhigh-resolution structure of a mAb (2-4) bound to RBD (FIG. 18A).Collectively, these findings will contribute to the understanding of howantibodies bind and neutralize SARS-CoV-2.

The potency and diversity of our SARS-CoV-2-neutralizing mAbs are likelyattributable to patient selection. Previously, we observed that infectedindividuals with severe disease developed a more robustvirus-neutralizing antibody response 25. If Patient 2 had not beenincluded, five of the top neutralizing mAbs would be lost. The diversityof our antibodies is also attributable, in part, to the choice of usingthe S trimer to sort from memory B cells, while most groups focused onthe use of RBD^(7,9-11,16-19,21). The characterization of this diversecollection of mAbs has allowed us to observe that all potentSARS-CoV-2-neutralizing antibodies described to date are directed to thetop of the viral spike. RBD and NTD are, no doubt, quite immunogenic.Neutralizing antibodies to the stem region of the S trimer remain to bediscovered. In conclusion, we believe several of our monoclonalantibodies with exquisite virus-neutralizing activity are promisingcandidates for development as modalities to treat or prevent SARS-CoV-2infection.

Methods

Expression and Purification of SARS-CoV-2 Proteins

The mammalian expression vector that encodes the ectodomain of theSARS-CoV-2 S trimer and the vector encoding RBD fused with SD1 at theN-terminus and an HRV-3C protease cleavage site followed by a mFc tagand an 8×His tag at the C-terminus were kindly provided by JasonMcLellan⁴. SARS-CoV-2 NTD (aa1-290) with an HRV-3C protease cleavagesite, a mFc tag, and an 8×His tag at the C-terminus was also cloned intomammalian expression vector pCAGGS. Each expression vector wastransiently transfected into Expi293 cells using 1 mg/mL ofpolyethylenimine (Polysciences). Five days post transfection, the Strimer was purified using Strep-Tactin XT Resin (Zymo Research), and theRBD-mFc and NTD-mFc were purified using protein A agarose (ThermoFisherScientific). In order to obtain RBD-SD1 and NTD, the mFc and 8×His tagsat the C-terminus were removed by HRV-3C protease (Millipore-Sigma) andthen purified using Ni-NTA resin (Invitrogen) followed by protein Aagarose.

Sorting for S Trimer-Specific B Cells and Single-Cell BCR Sequencing

Peripheral blood mononuclear cells from five patients and one healthydonor were stained with LIVE/DEAD™ Fixable Yellow Dead Cell Stain Kit(Invitrogen) at ambient temperature for 20 mins, followed by washingwith RPMI-1640 complete medium and incubation with 10 μg/mL of S trimerat 4° C. for 45 mins. Afterwards, the cells were washed again andincubated with a cocktail of flow cytometry and hashtag antibodies,containing CD3 PE-CF594 (BD Biosciences), CD19 PE-Cy7 (Biolegend), CD20APC-Cy7 (Biolegend), IgM V450 (BD Biosciences), CD27 PerCP-Cy5.5 (BDBiosciences), anti-His PE (Biolegend), and human Hashtag 3 (Biolegend)at 4° C. for 1 hr. Stained cells were then washed, resuspended inRPMI-1640 complete medium and sorted for S trimer-specific memory Bcells (CD3-CD19+CD27+S trimer+live single lymphocytes). The sorted cellswere mixed with mononuclear cells from the same donor, labeled withHashtag 1, and loaded into the 10× Chromium chip of the 5′ Single CellImmune Profiling Assay (10× Genomics) at the Columbia University HumanImmune Monitoring Core (HIMC; RRID:SCR_016740). The library preparationand quality control were performed according to manufacturer's protocoland sequenced on a NextSeq 500 sequencer (Illumina).

Identification of S Trimer-Specific Antibody Transcripts

For each sample, full-length antibody transcripts were assembled usingthe VDJ module in Cell Ranger (version 3.1.0, 10× Genomics) with defaultparameters and the GRCh38 genome as reference. To identify cells fromthe antigen sort, we first used the count module in Cell Ranger tocalculate copies of all hashtags in each cell from the Illumina NGS rawreads. High confidence antigen-specific cells were identified asfollows. Briefly, based on the copy numbers of the hashtags observed, acell must contain more than 100 copies of the antigen sort-specifichashtag to qualify as an antigen-specific cell. Because hashtags canfall off from cells and bind to cells from a different population in thesample mixture, each cell usually has both sorted and spiked-in-specifichashtags. To enrich for true antigen-specific cells, the copy number ofthe specific hashtag has to be at least 1.5× higher than that of thenon-specific hashtag. Low quality cells were identified and removedusing the cell-calling algorithm in Cell Ranger. Cells that do not haveproductive H and L chain pairs were excluded. If a cell contains morethan two H or/and L chain transcripts, the transcripts with less than 3unique molecular identifiers were removed. Cells with identical H and Lchain sequences, which may have resulted from mRNA leakage, were mergedinto one cell. Additional filters were applied to remove low qualitycells and/or transcripts in the antibody gene annotation process.

Antibody Transcript Annotation and Selection Criteria

Antigen-specific antibody transcripts were processed using ourbioinformatics pipeline SONAR for quality control and annotation²⁶.Briefly, V(D)J genes were assigned for each transcript using BLAST²⁷with customized parameters against a germline gene database obtainedfrom the international ImMunoGeneTics information system (IMGT)database^(26,28). Based on BLAST alignments of V and J regions, CDR3 wasidentified using the conserved second cysteine in the V region and WGXG(H chain) or FGXG (L chain) motifs in the J region (X represents anyamino acid). For H chain transcripts, the constant domain 1 (CH1)sequences were used to assign isotype using BLAST with defaultparameters against a database of human CH1 genes obtained from IMGT. ABLAST E-value threshold of 1 E-6 was used to find significant isotypeassignments, and the CH1 allele with the lowest E-value was used.Sequences other than the V(D)J region were removed and transcriptscontaining incomplete V(D)J or/and frame shift were excluded. We thenaligned each of the remaining transcripts to the assigned germline Vgene using CLUSTALO²⁹ and calculated the somatic hypermutation level.

To select representative antibodies for functional characterization, wefirst clustered all antibodies using USEARCH³⁰ with the followingcriteria: identical heavy chain V and J gene assignments, the samelength of CDRH3, and CDRH3 identity higher than 0.9. For each cluster,cells with the same light chain V and J gene assignments were groupedinto a clone. All clone assignments were manually checked. We thencalculated the clonal size for each clone, and one H and L chain pairper clone was chosen for antibody synthesis. For clones with multiplemembers, the member with the highest somatic hypermutation level waschosen for synthesis. For cells having multiple high quality H or Lchains, which may be from doublets, we synthesized all H and L chaincombinations.

Analysis of S Trimer-Specific Antibody Repertoire

Because 88% of the S trimer-specific antibodies were IgG isotype, wetherefore compared the repertoire features to IgG repertoires from threehealthy donors³¹ (17,243 H chains, 27,575 kappa L chains, 20,889 lambdaL chains). The repertoire data from the three healthy donors werecombined and annotated using SONAR with the same process as above.

Antibody Expression and Purification

For each antibody, variable genes were optimized for human cellexpression and synthesized by GenScript. VH and VL were insertedseparately into plasmids (gWiz or pcDNA3.4) that encode the constantregion for H chain and L chain. Monoclonal antibodies were expressed inExpi293 (ThermoFisher, A14527) by co-transfection of H chain and L chainexpressing plasmids using polyethylenimine and culture in 37° C. shakerat 125 RPM and 8% CO2. On day 3 post transfection, 400 μL of supernatantwere collected for screening for binding to S trimer and RBD by ELISA,and for neutralization of SARS-CoV-2 pseudovirus and authentic virus.Supernatants were also collected on day 5 for antibody purification byrProtein A Sepharose (GE, 17-1279-01) affinity chromatography.

Production of Pseudoviruses

Recombinant Indiana VSV (rVSV) expressing SARS-CoV-2 spike was generatedas previouslydescribed32,33. HEK293T cells were grown to 80% confluencybefore transfection with pCMV3-SARS-CoV-2-spike (Sino Biological) usingFuGENE 6 (Promega). Cells were cultured overnight at 37° C. with 5% CO2.The next day, medium was removed and VSV-G pseudotyped ΔG-luciferase(G*ΔG-luciferase, Kerafast) was used to infect the cells in DMEM at aMOI of 3 for 1 hr before washing the cells with 1×DPBS three times. DMEMsupplemented with 2% fetal bovine serum and 100 I.U./mL of penicillinand 100 μg/mL of streptomycin were added to the inoculated cells, whichwere cultured overnight as described above. The supernatant washarvested the following day and clarified by centrifugation at 300 g for10 mins before aliquoting and storing at −80° C.

Pseudovirus Neutralization

Neutralization assays were performed by incubating pseudoviruses withserial dilutions of heat inactivated plasma together with supernatant orpurified antibodies, and scored by the reduction in luciferase geneexpression. In brief, Vero E6 cells (ATCC) were seeded in a 96-wellplate at a concentration of 2×104 cells per well. Pseudoviruses wereincubated the next day with serial dilutions of the test samples induplicate or triplicate for 30 mins at 37° C. The mixture was added tocultured cells and incubated for an additional 24 hrs. The luminescencewas measured by Britelite plus Reporter Gene Assay System (PerkinElmer).IC₅₀ was defined as the dilution at which the relative light units werereduced by 50% compared with the virus control wells (virus+cells) aftersubtraction of the background in the control groups with cells only. TheIC₅₀ values were calculated using non-linear regression in GraphPadPrism 8.0.

Authentic SARS-CoV-2 Neutralization

Supernatants containing expressed mAbs were diluted 1:10 and 1:50 inEMEM with 7.5% inactivated fetal calf serum and incubated with authenticSARS-CoV-2 (strain USA-WA1/2020; MOI 0.1) for 1 hr at 37° C.Post-incubation, the mixture was transferred onto a monolayer of Vero E6cells that was cultured overnight. After incubation of the cells withthe mixture for 70 hrs at 37° C., cytopathic effects (CPE) caused by theinfection were scored for each well from 0 to 4 to indicate the degreeof virus inhibition. Semi-quantitative representation of the inhibitionfor each antibody-containing supernatant at a dilution of 1:50 is shownin the lowest panel of FIG. 15B with neutralization levels ranging from(−) for none to (+++) for complete neutralization.

An end-point dilution assay in a 96-well plate format was performed tomeasure the neutralization activity of select purified mAbs. In brief,each antibody was serially diluted (5-fold dilutions) starting at 20μg/mL. Triplicates of each mAb dilution were incubated with SARS-CoV-2at aMOI of 0.1 in EMEM with 7.5% inactivated fetal calf serum for 1 hrat 37° C. Post incubation, the virus-antibody mixture was transferredonto a monolayer of Vero-E6 cells grown overnight. The cells wereincubated with the mixture for 70 hrs. CPE were visually scored for eachwell in a blinded fashion by two independent observers. The results werethen converted into percentage neutralization at a given mAbconcentration, and the averages ±SEM were plotted using a five-parameterdose-response curve in GraphPad Prism 8.0.

Epitope Mapping by ELISA

50 ng/well of S trimer, 50 ng/well of RBD, and 100 ng/well of NTD werecoated on ELISA plates at 4° C. overnight. The ELISA plates were thenblocked with 300 μL of blocking buffer (1% BSA and 10% bovine calf serum(BCS) (Sigma) in PBS at 37° C. for 2 hrs. Afterwards, supernatants fromthe antibody transfection or purified antibodies were serially dilutedusing dilution buffer (1% BSA and 20% BCS in PBS), incubated at 37° C.for 1 hr. Next, 100 μL of 10,000-fold diluted Peroxidase AffiniPure goatanti-human IgG (H+L) antibody (Jackson ImmunoResearch) were added intoeach well and incubated for 1 hr at 37° C. The plates were washedbetween each step with PB ST (0.5% Tween-20 in PBS). Finally, the TMBsubstrate (Sigma) was added and incubated before the reaction wasstopped using 1M sulfuric acid. Absorbance was measured at 450 nm.

For the competition ELISA, purified mAbs were biotin-labeled usingOne-Step Antibody Biotinylation Kit (Miltenyi Biotec) followingmanufacturer recommendations and purified using 40K MWCO DesaltingColumn (ThermoFisher Scientific). 50 μL of serially diluted competitorantibodies were added into S trimer-precoated ELISA plates, followed byμL of biotinylated antibodies at a concentration that achieves an OD450reading of 1.5 in the absence of competitor antibodies. Plates wereincubated at 37° C. for 1 hr, and 100 μL of 500-fold diluted Avidin-HRP(ThermoFisher Scientific) were added into each well and incubated foranother 1 hr at 37° C. The plates were washed by PBST between each ofthe previous steps. The plates were developed afterwards with TMB andabsorbance was read at 450 nm after the reaction was stopped.

For the ACE2 competition ELISA, 100 ng of ACE2 protein (Abcam) wasimmobilized on the plates at 4° C. overnight. The unbound ACE2 waswashed away by PB ST and then the plates were blocked. After washing,100 ng of S trimer in 50 μL of dilution buffer was added into each well,followed by adding another 50 μL of serially diluted competitorantibodies and then incubating the plates at 37° C. for 1 hr. The ELISAplates were washed 4 times by PBST and then 100 μL of 2000-fold dilutedanti-strep-HRP (Millipore Sigma) were added into each well for another 1hr at 37° C. The plates were then washed, developed with TMB, andabsorbance was read at 450 nm after the reaction was stopped.

For all the competition ELISA experiments, the relative binding ofbiotinylated antibodies or ACE2 to the S trimer in the presence ofcompetitors was normalized by comparing to competitor-free controls.Relative binding curve and the area under curve (AUC) were generated byfitting the non-linear five-parameter dose-response curve in GraphPadPrism 8.0.

Cell-Surface Competition Binding Assay

Expi293 cells were co-transfected with vectors encodingpRRL-cPPT-PGK-GFP (Addgene) and pCMV3-SARS-CoV-2 (2019-nCoV) Spike (SinoBiological) at a ratio of 1:1. Two days after transfection, cells wereincubated with a mixture of biotinylated mAb 2-43 (0.25 μg/mL) andserially diluted competitor antibodies at 4° C. for 1 hr. Then 100 μL ofdiluted APC-streptavidin (Biolegend) were added to the cells andincubated at 4° C. for 45 mins. Cells were washed 3 times with FACSbuffer before each step. Finally, cells were resuspended and 2-43binding to cell-surface S trimer was quantified on LSRII flow cytometer(BD Biosciences). The mean fluorescence intensity of APC in GFP-positivecells was analyzed using FlowJo and the relative binding of 2-43 to Strimer in the presence of competitors was calculated as the percentageof the mean fluorescence intensity compared to that of thecompetitor-free controls.

Cryo-EM Data Collection and Processing

SARS-CoV-2 S trimer at a final concentration of 2 mg/ml was incubatedwith 6-fold molar excess per spike monomer of the antibody Fab fragmentsfor 30 mins in 10 mM Tris-HCl, 150 mM NaCl, and 0.005%n-Dodecyl-β-D-maltoside (DDM). 2 μL of sample were incubated on C-flat1.2/1.3 carbon grids for 30 secs and vitrified using a Leica EM GPPlunge Freezer. Data were collected on a Titan Krios electron microscopeoperating at 300 kV equipped with a Gatan K3 direct detector and energyfilter using the Leginon software package34. A total electron fluence of51.3 e/Å2 was fractionated over 40 frames, with a total exposure time of2 secs. A magnification of 81,000× resulted in a pixel size of 1.058 Å,and a defocus range of −0.4 to −3.5 μm was used. All processing was doneusing cryoSPARC v2.14.235. Raw movies were aligned and dose-weightedusing patch motion correction, and the CTF was estimated using patch CTFestimation. A small subset of approximately 200 micrographs were pickedusing blob picker, followed by 2D classification and manual curation ofparticle picks, and used to train a Topaz neural network³⁶. This networkwas then used to pick particles from the remaining micrographs, whichwere extracted with a box size of 384 pixels. For the Fab 2-4 dataset,2D classification followed by ab initio modelling and 3D heterogeneousrefinement revealed 83,927 particles with three 2-4 Fabs bound, one toeach RBD. Our construction of these particles using Non-UniformRefinement with imposed C3 symmetry resulted in a 3.6 Å map, asdetermined by the gold standard FSC. Given the relatively low resolutionof the RBD-Fab interface, masked local refinement was used to obtain a3.5 Å map with significantly improved density. A masked local refinementof the remainder of the S timer resulted in a 3.5 Å reconstruction.These two local refinements were aligned and combined using the vopmaximum function in UCSF Chimera³⁷. This was repeated for the half maps,which were used, along with the refinement mask from the globalNon-Uniform refinement, to calculate the 3DFSC38 and obtain an estimatedresolution of 3.2 Å. All maps have been submitted to the EMDB with theID EMD-22156. For the Fab 4-8 dataset, image preprocessing and particlepicking was performed as above. 2D classification, ab initio modelling,and 3D heterogeneous classification revealed 47,555 particles with 3Fabs bound, one to each NTD and with all 3 RBDs in the downconformation. While this particle stack was refined to 3.9 Å usingNon-Uniform refinement with imposed C3 symmetry, significant molecularmotion prevented the visualization of the Fab epitope at high resolution(EMD-22159). In addition, 105,278 particles were shown to have 3 Fabsbound, but with 1 RBD in the up conformation. These particles wererefined to 4.0 Å using Non-Uniform refinement with Cl symmetry(EMD-22158), and suffered from the same conformational flexibility asthe all-RBD-down particles. This flexibility was visualized using 3Dvariability analysis in cryoSPARC. For the Fab 2-43 dataset, which wascollected at an electron fluence of 53.4 e/Å2, image preprocessing andparticle picking was performed as above, save that motion correction wasperformed using MotionCor239. 2D classification, ab initio modelling,and 3D heterogeneous classification revealed 18,884 particles with 3Fabs bound, which was refined to 7.8 Å resolution 601 (EMD-22157).

Cryo-EM Model Fitting

An initial homology model of the 2-4 Fab was built using SchrodingerRelease 2020-2: BioLuminate⁴⁰. The RBD was initially modeled using thecoordinates from PDB ID 6W41. The remainder of the S timer was modeledusing the coordinates from PDB ID 6VSB. These models were docked intothe consensus map using Chimera. The model was then fitted interactivelyusing ISOLDE 1.0b541 and COOT 0.8.9.242, and using real space refinementin Phenix 1.1843. In cases where side chains were not visible in theexperimental data, they were truncated to alanine. Validation wasperformed using Molprobity⁴⁴ and EMRinger⁴⁵. The model was submitted tothe PDB with the ID 6XEY. Figures were prepared using ChimeraX⁴⁶.

References for Example 10

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Example 11—Potent Neutralizing Monoclonal Antibodies

FIGS. 32A-B show monoclonal antibody 2-15mut. FIG. 32A shows virusneutralization with the 2-15mut antibody. FIG. 32B shows potency of the2-15mut antibody. The 2-15mut antibody displays an IC₅₀ concentration ofless than 0.00064 μg/ml and an IC₉₀ concertation of 0.011 μg/ml.

FIGS. 33A-B show select mutants of the 4-8 monoclonal antibody. FIG. 33Ashows neutralization with antibodies 4-8 (39/51) and 4-8(39/51/57). FIG.33B shows potency of antibodies 4-8 (39/51) and 4-8(39/51/57). The4-8(39/51) antibody displays an IC₅₀ concentration of 0.002 μg/ml and anIC₉₀ concertation of 0.108 μg/ml. The 4-8(39/51/57) antibody displays anIC₅₀ concentration of 0.003 μg/ml and an IC₉₀ concertation of 0.014μg/ml.

FIG. 34 shows a summary of IC₅₀ and IC₉₀ values of selected monoclonalantibody mutants.

Example 12—Identification and Characterization of a Cross-NeutralizingMonoclonal Antibody 2-36

SARS-CoV-2 is phylogenetically closely related to SARS-CoV, which causedthe 2002-2003 human epidemic. SARS-CoV and SARS-CoV-2 share 76% aminoacid identity in their Spike proteins, raising the possibility ofconserved immunogenic surfaces on these antigens. Many human monoclonalantibodies have now been shown to target the SARS-CoV-2 Spike protein,but cross-neutralizing antibodies are relatively uncommon in individualswith COVID-19. There are also SARS-like viruses including some zoonoticsarbecoviruses in bats or pangolins which could infect human cells, andtherefore, have the potential to cause next pandemics.

Our invention claims to isolate and characterize a monoclonal antibodythat could not only neutralize SARS-CoV-2 and SARS-CoV but alsoneutralize sarbecoviruses in bats and pangolins. Such cross-neutralizingantibodies are extremely valuable to understand how to confer broaderprotection against human SARS-like viruses that include the extensivereservoir of zoonotic sarbecoviruses in bats, pangolins, etc.

In order to find antibodies that have cross-neutralizing activities, wescreened anti-SARS-CoV antibodies from COVID-19 convalescent patients.SARS-CoV-2 spike specific antibodies were isolated by single-B cellsorting and 10× genomics sequencing, and then the antibodies weresynthesized and the transfection supernatants were used to screenanti-SARS-CoV antibodies using SARS-CoV pseudovirus. While most of theantibodies showed no or very weak neutralizing activity, antibody 2-36was found to be a potent neutralizer against SARS-CoV (FIG. 35 ).

We next characterized this antibody by first testing its binding toSARS-CoV-2 and SARS-CoV spikes by ELISA with CR3022, an antibodypreviously reported to have cross-activity, as a control. We confirmedthat antibody 2-36 can bind to both SARS-CoV-2 and SARS-CoV spikes(FIGS. 36A-B). We then measured the binding affinity of antibody 2-36 tothose spikes by SPR and we further confirmed that antibody 2-36 can bindto both SARS-CoV-2 (FIG. 37A) and SARS-CoV (FIG. 37B) spikes but with ahigher affinity to SARS-CoV-2 spike. As a control, the SARS-CoV-2specific antibody 2-4 only binds only to SARS-CoV-2 spike but not toSARS-CoV spike (FIGS. 37C-D).

We then tested the neutralization activity of antibody 2-36 againstSARS-CoV-2 and SARS-CoV, and showed that antibody 2-36 can potentlyneutralize SARS-CoV-2 with IC₅₀ 0.004 μg/ml (FIG. 38A). Antibody 2-36also neutralized SARS-CoV, but with a lower potency, IC₅₀ 0.386 μg/ml(FIG. 38B). The control antibody CR3022 neutralizes SARS-CoV but veryweakly on SARS-CoV-2; and antibody 2-4 only neutralizes SARS-CoV-2(FIGS. 38A-B).

We also tested antibody 2-36 against a panel of other coronavirusesincluding, MERS-CoV, human common cold coronavirus 229E and some bat andpangolin coronaviruses (FIG. 39A) including 6 among the SARS-CoV-relatedlineage (e.g., WIV1, SHC014, LYRa11, Rs7327, Rs4231, Rs4084) and 3 inthe SARS-CoV-2-related lineage (e.g., RaTG13, GDPangolin, GXPangolin).Pseudoviruses with the spikes of these coronaviruses were made andtested. As shown in FIG. 39B, antibody 2-36 neutralized SARS-CoV andSARS-CoV-2 and their related lineage viruses, but did not neutralizeMERS-CoV and 229E, indicating its breadth.

We also solved the Cryo-EM structure of antibody 2-36 in complex withSARS-CoV-2 Spike trimer (FIG. 40A), which showed in detail how theantibody interact with spike (FIG. 40B). 2-36 binds to the side of theRBD and can compete with ACE2 for RBD binding, although its epitope doesnot overlap the ACE2-binding site (FIG. 40C). The 2-36 epitope on thespike is highly conserved among SARS-CoV-2, SARS-CoV, and otherSARS-related coronaviruses (FIG. 40D), which could explain why 2-36showed such broad neutralizing properties.

As such, antibody 2-36 can serve as the starting point for engineering amore potent antibody against diverse bat coronaviruses with humanpandemic potential. Such an antibody could be further developed andplaced in the national stockpile for pandemic preparedness. Furthermore,we have a defined a conserved site in the spike that could be targetedfor development of a broadly protective vaccine against batcoronaviruses with pandemic potential.

Example 13 Monoclonal Antibody Number 2-36

Antibody 2-36 is a monoclonal antibody that neutralizes SARS-CoV-2variants, SARS-CoV, and other beta-coronaviruses. To screen monoclonalantibodies with cross-neutralizing activity against otherbeta-coronaviruses, more than 200 mAbs isolated from COVID-19convalescent patients (Liu et al. Nature 2020) were tested on SARS-CoVpseudovirus. Monoclonal antibody 2-36 not only neutralizes SARS-CoV-2pseudovirus at IC₅₀˜0.04 μg/ml and authentic virus at IC₅₀˜0.1 μg/mL,but also shows neutralizing activity against SARS-CoV, although withlower potency (IC₅₀˜0.2 μg/mL on pseudovirus and IC₅₀˜7.5 μg/mL onauthentic virus). Monoclonal antibody 2-36 can block SARS-CoV-2 spiketrimer binding to ACE2. Conservation analysis on the receptor-bindingdomain (RBD) among SARS-CoV-2, SARS-CoV, and some bat and pangolincoronavirus strains show that the 2-36 binding site is highly conserved.Antibody 2-36 was tested on different SARS-CoV-2 variants ofconcern/interest (including B.1.1.7, B.1.351, P.1, B.1.526, R.1,B.1.429) and many single mutations with high circulating frequency. Theresults show that antibody 2-36 can neutralize all thesevariants/mutations without any significant loss of activities. Moreover,besides SARS-CoV-2 and SARS-CoV, antibody 2-36 also neutralizes some batand pangolin coronaviruses which can use human ACE2 as a receptor toenter host cells. These coronaviruses include but are not limited toRaTG13, WIV1, SHC014, GDPangolin, and GXPangolin viruses. Antibody 2-36escape mutations were selected by in vitro passage of SARS-CoV-2 in VeroE6 cells in presence of 2-36 and confirmed that K378T in spike RBD, withvery low frequency in nature, led to viral resistance. Taken theseresults together, 2-36 represents a promising strategic reserve drugcandidate for the prevention and treatment of possible diseases causedby pre-emergent SARS-related CoVs.

FIGS. 90A-D show virus neutralization with monoclonal antibody 2-36.FIG. 90A shows screening of transfection supernatant for neutralizationactivity against SARS-CoV-2 pseudovirus. FIG. 90B shows screening oftransfection supernatant for neutralization activity against SARS-CoVpseudovirus. FIG. 90C shows 2-36 neutralization IC₅₀ (μg/mL) againstSARS-CoV-2 pseudovirus (PV) and live virus (LV). FIG. 90D shows 2-36neutralization IC₅₀ (μg/mL) against SARS-CoV pseudovirus (PV) and livevirus (LV).

FIGS. 91A-B show binding of monoclonal antibody 2-36 to SARS-CoV-2 (FIG.91A) and SARS-CoV (FIG. 91B) spike as determined by ELISA.

FIGS. 92A-H show binding affinity for monoclonal antibodies 2-36 and 2-4to SARS-CoV-2 and SARS-CoV viruses as measured by SPR. FIG. 92A shows2-36 binding affinity to SARS-CoV-2 spike protein. FIG. 92B shows 2-4binding affinity to SARS-CoV-2 spike protein. FIG. 92C shows 2-36binding affinity to SARS-CoV spike protein. FIG. 92D shows 2-4 bindingaffinity to SARS-CoV spike protein. FIG. 92E shows 2-36 binding affinityto SARS-CoV-2 receptor binding domain (RBD). FIG. 92F shows 2-4 bindingaffinity to SARS-CoV-2 RBD. FIG. 92G shows 2-36 binding affinity toSARS-CoV RBD. FIG. 92H shows 2-4 binding affinity to SARS-CoV RBD.

FIGS. 93A-B show binding to SARS-CoV-2 spike protein. FIG. 93A showsthat binding of monoclonal antibody 2-36 to SARS-CoV-2 spike isinhibited by CR3022. FIG. 93B shows that monoclonal antibody 2-36inhibits hACE2 binding to SARS-CoV-2 spike protein.

FIG. 94 shows conservation analysis on the RBD among SARS CoV-2, SARSCoV-1, Bat CoVs, and Human CoVs virus strains. The analysis shows thatthe 2-36 binding site is highly conserved; with regions of highconservation in grey and low conservation in red. The 2-36 binding siteis outlined in blue.

FIGS. 95A-D show that monoclonal antibody 2-36 neutralizes SARS-CoV-2variants and SARS-like coronaviruses using hACE2. FIG. 95A showsneutralization against live variants. FIG. 95B shows neutralizationagainst pseudovariants. FIG. 95C shows evolution tree of viruses. FIG.95D shows antibody potency against viruses.

FIGS. 96A-D shows that monoclonal antibody 2-36 neutralizes SARS-likecoronaviruses using hACE2. FIG. 96A shows virus neutralization with 2-36antibody. FIG. 96B shows virus neutralization with S309 antibody. FIG.96C shows virus neutralization with COVA1-16 antibody. FIG. 96D showsvirus neutralization with CR3022 antibody.

FIGS. 97A-D show in vitro selection of 2-36 antibody escape mutations.FIG. 97A shows evolution of escape mutations during in vitro passage ofSARS-CoV-2 USA/WA1 in Vero E6 cells in the presence of 2-36. FIG. 97Bshows 2-36 neutralization activity tested against virus passages. FIG.97C shows spike protein with selected mutation localized. FIG. 97D showsthat the selected escape mutations were introduced into pseudovirusesand then 2-36 neutralization activity was tested against these viruses.

Examples for Bispecific Antibodies

As described herein, bispecific antibodies bearing either the 1400 armor the A32 arm indicate that those arms of the bispecific antibody arenot specific to and do not bind the spike protein of the SARS-CoV-2virus. These antibodies provide an “irrelevant” control to demonstratethe need for avidity by “both” arms of bispecific antibodies beingcontrolled for. Constructs bearing these irrelevant controls arereferred to as single arm IgG controls. 1400 (PGDM1400) is aneutralizing monoclonal antibody against the human immunodeficiencyvirus (HIV). A32 is a non-neutralizing monoclonal antibody against HIV.The same control antibodies were used throughout the study. AbX and AbYare controls, X=PGDM1400 (HIV neutralization antibody). Y=A32 (HIVneutralization antibody). Because they do not neutralize SARS-CoV-2 orany variant strains, they are utilized herein to construct bispecificantibodies with one arm against SARS-CoV-2 and the other arm without anyactivity against SARS-CoV-2. These control antibodies, therefore, allowone to accurately attribute the contribution of each arm to the activityof the bispecific antibodies.

Example 14

FIG. 42 shows that the 2-17/1-57 bispecific antibody against SARS-CoV-2does not enhance potency compared to respective single arm counterpart.Ab X and Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the2-17/1-57 bispecific antibody is 0.023 μg/mL. The IC₉₀ of the 2-17/1-57bispecific antibody is 0.167 μg/mL. The IC₅₀ of the Ab X/1-57 control is0.014 μg/mL. The IC₉₀ of the Ab X/1-57 control is 0.424 μg/mL. The IC₅₀of the 2-17/Ab Y control is 1.451 μg/mL. The IC₉₀ of the 2-17/Ab Ycontrol is 3.572 μg/mL.

FIG. 43 shows potent neutralization of bispecific antibody 2-17/2-7against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the2-17/2-7 bispecific antibody is 0.008 μg/mL. The IC₉₀ of the 2-17/2-7bispecific antibody is 0.025 μg/mL. The IC₅₀ of the Ab X/2-7 control is0.028 μg/mL. The IC₉₀ of the Ab X/2-7 control is 0.162 μg/mL. The IC₅₀of the 2-17/Ab Y control is 1.451 μg/mL. The IC₉₀ of the 2-17/Ab Ybispecific antibody is 3.572 μg/mL.

FIG. 44 shows potent neutralization of bispecific antibody 2-17/2-15against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the2-17/2-15 bispecific antibody is 0.006 μg/mL. The IC₉₀ of the 2-17/2-15bispecific antibody is 0.085 μg/mL. The IC₅₀ of the Ab X/2-15 control is0.043 μg/mL. The IC₉₀ of the Ab X/2-15 bispecific antibody is 0.232μg/mL. The IC₅₀ of the 2-17/Ab Y control is 1.451 μg/mL. The IC₉₀ of the2-17/Ab Y control is 3.572 μg/mL.

FIG. 45 shows potent neutralization of bispecific antibody 2-17/2-30against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the2-17/2-30 bispecific antibody is 0.065 μg/mL. The IC₉₀ of the 2-17/2-30bispecific antibody is 0.598 μg/mL. The IC₅₀ of the Ab X/2-30 control is0.349 μg/mL. The IC₉₀ of the Ab X/2-30 control is 4.939 μg/mL. The IC₅₀of the 2-17/Ab Y control is 1.451 μg/mL. The IC₉₀ of the 2-17/Ab Ycontrol is 3.572 μg/mL.

FIG. 46 shows potent neutralization of bispecific antibody 2-17/4-20against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the2-17/4-20 bispecific antibody is 0.030 μg/mL. The IC₉₀ of the 2-17/4-20bispecific antibody is 0.164 μg/mL. The IC₅₀ of the Ab X/4-20 control is0.084 μg/mL. The IC₉₀ of the Ab X/4-20 control is 3.066 μg/mL. The IC₅₀of the 2-17/Ab Y control is 1.451 μg/mL. The IC₉₀ of the 2-17/Ab Ycontrol is 3.572 μg/mL.

FIG. 47 shows potent neutralization of bispecific antibody 5-24/1-57against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the5-24/1-57 bispecific antibody is 0.004 μg/mL. The IC₉₀ of the 5-24/1-57bispecific antibody is 0.046 μg/mL. The IC₅₀ of the Ab X/1-57 control is0.014 μg/mL. The IC₉₀ of the Ab X/1-57 control is 0.424 μg/mL. The IC₅₀of the 5-24/Ab Y control is 0.137 μg/mL. The IC₉₀ of the 5-24/Ab Ycontrol is 2.320 μg/mL.

FIG. 48 shows potent neutralization of bispecific antibody 5-24/2-15against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the5-24/2-15 bispecific antibody is 0.004 μg/mL. The IC₉₀ of the 5-24/2-15bispecific antibody is 0.033 μg/mL. The IC₅₀ of the Ab X/2-15 control is0.043 μg/mL. The IC₉₀ of the ab X/2-15 control is 0.232 μg/mL. The IC₅₀of the 5-24/Ab Y control is 0.137 μg/mL. The IC₉₀ of the 5-24/Ab Ycontrol is 2.320 μg/mL.

FIG. 49 shows bispecific antibody 5-24/4-20 against SARS-CoV-2 does notenhance potency (IC₅₀) compared to respective single arm counterpart. AbX and Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the5-24/4-20 bispecific antibody is 0.063 μg/mL. The IC₉₀ of the 5-24/4-20bispecific antibody is 0.222 μg/mL. The IC₅₀ of the Ab X/4-20 control is0.084 μg/mL. The IC₉₀ of the Ab X/4-20 control is 3.066 μg/mL. The IC₅₀of the 5-24/Ab Y control is 0.137 μg/mL. The IC₉₀ of the 5-24/Ab Ycontrol is 2.320 μg/mL.

FIG. 50 shows potent neutralization of bispecific antibody 1-20/1-68against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm Ab). The IC₅₀ of the 1-20/1-68 bispecificantibody is 0.010 μg/mL. The IC₉₀ of the 1-20/1-68 bispecific antibodyis 0.157 μg/mL. The IC₅₀ of the 1-20/Ab Y control is 0.078 μg/mL. TheIC₉₀ of the 1-20/Ab Y control is 1.241 μg/mL. The IC₅₀ of the Ab X/1-68control is 0.035 μg/mL. The IC₉₀ of the Ab X/1-68 control is 0.332μg/mL.

FIG. 51 shows potent neutralization of bispecific antibody 1-20/2-17against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the1-20/2-17 bispecific antibody is 0.025 μg/mL. The IC₉₀ of the 1-20/2-17bispecific antibody is 0.213 μg/mL. The IC₅₀ of the 1-20/Ab Y control is0.078 μg/mL. The IC₉₀ of the 1-20/Ab Y control is 1.241 μg/mL. The IC₅₀of the Ab X/2-17 control is 0.380 μg/mL. The IC₉₀ of the Ab X/2-17control is 3.912 μg/mL.

FIG. 52 shows potent neutralization of bispecific antibody 1-20/4-18against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the1-20/4-18 bispecific antibody is 0.009 μg/mL. The IC₉₀ of the 1-20/4-18bispecific antibody is 0.043 μg/mL. The IC₅₀ of the 1-20/Ab Y control is0.078 μg/mL. The IC₉₀ of the 1-20/Ab Y control is 1.241 μg/mL. The IC₅₀of the Ab X/4-18 control is 0.049 μg/mL. The IC₉₀ of the Ab X/4-18control is 3.463 μg/mL.

FIG. 53 shows potent neutralization of bispecific antibody 1-20/5-24against SARS-CoV-2 compared to respective single arm counterpart. Ab Xand Ab Y are single arm irrelevant controls. X=PGDM1400 (HIVneutralization Ab). Y=A32 (HIV neutralization Ab). The IC₅₀ of the1-20/5-24 bispecific antibody is 0.009 μg/mL. The IC₉₀ of the 1-20/5-24bispecific antibody is 0.035 μg/mL. The IC₅₀ of the 1-20/Ab Y control is0.078 μg/mL. The IC₉₀ of the 1-20/Ab Y control is 1.241 μg/mL. The IC₅₀of the Ab X/5-24 control is 0.500 μg/mL. The IC₉₀ of the Ab X/5-24control is 4.120 μg/mL.

Constructed bispecific antibodies show potent neutralization againstSARS-CoV-2 at a level similar or better than the parental antibodies.Both arms of the bispecific antibodies contribute to the neutralizationactivity of the bispecific molecule. A bispecific antibody is a singlemolecule with high barrier for viral escape and/or synergetic potencyfor COVID-19 treatment and prevention. Activity enhancement observed canbe extended to any engineered bispecific antibody format.

FIG. 54 shows potent neutralization against SARS-CoV-2. Bispecificantibodies with 2-17 as a component are more potent than the single armcontrol (2-17/A32, A32 is a control antibody show no activity againstSARS-CoV-2), indicating that the other arm targeting the different viralepitope together with the 2-17 arm are contributing to the overallneutralization activity of the bispecific molecule. FIG. 54 shows IC₅₀and IC₉₀ values for 2-17-containing bispecific antibodies.

FIG. 55 shows potent neutralization against SARS-CoV-2 with bispecificantibodies containing 5-24 as a component. FIG. 55 shows IC₅₀ and IC₉₀values for 5-24-containing bispecific antibodies.

FIG. 56 shows potent neutralization against SARS-CoV-2 with bispecificantibodies containing 1-20 as a component. FIG. 56 shows IC₅₀ and IC₉₀values for 1-20—containing bispecific antibodies.

Example 15

FIGS. 57A-E show bispecific antibodies with 1-20 (RBD) as a parentalantibody. FIG. 57A shows virus neutralization with bispecific antibodies1-20/5-24, 1-20/4-18, 1-20/2-17, and 1-20/1-68. FIG. 57B shows virusneutralization with the bispecific antibody 1-20/5-24 compared tocontrol antibodies. FIG. 57C shows virus neutralization with thebispecific antibody 1-20/4-18 compared to control antibodies. FIG. 57Dshows virus neutralization with the bispecific antibody 1-20/2-17compared to control antibodies. FIG. 57E shows virus neutralization withthe bispecific antibody 1-20/1-68 compared to control antibodies.Control antibodies were generated using irrelevant antibody such asPGDM1400 (Ab X) or A32 (Ab Y) replacing one arm of the bispecificantibody.

FIG. 58 shows potencies of bispecific antibodies with 1-20 (RBD) as aparental antibody. The IC₅₀ of bispecific antibody 1-20/5-24 is 0.009μg/ml. The IC₉₀ of bispecific antibody 1-20/5-24 is 0.035 μg/ml. TheIC₅₀ of bispecific antibody 1-20/4-18 is 0.009 μg/ml. The IC₉₀ ofbispecific antibody 1-20/4-18 is 0.043 μg/ml. The IC₅₀ of bispecificantibody 1-20/2-17 is 0.025 μg/ml. The IC₉₀ of bispecific antibody1-20/2-17 is 0.212 μg/ml. The IC₅₀ of bispecific antibody 1-20/1-68 is0.009 μg/ml. The IC₉₀ of bispecific antibody 1-20/1-68 is 0.028 μg/ml.

FIGS. 59A-G show bispecific antibodies with 2-17 (NTD) as a parentalantibody. FIG. 59A shows virus neutralization with bispecific antibodies2-17/2-7, 2-17/1-57, 2-36/2-17, 2-17/4-20, 2-17/2-30, and 2-17/2-15.FIG. 59B shows virus neutralization with the bispecific antibody2-17/2-7 compared to control antibodies. FIG. 59C shows virusneutralization with the bispecific antibody 2-17/1-57 compared tocontrol antibodies. FIG. 59D shows virus neutralization with thebispecific antibody 2-17/2-15 compared to control antibodies. FIG. 59Eshows virus neutralization with the bispecific antibody 2-17/4-20compared to control antibodies. FIG. 59F shows virus neutralization withthe bispecific antibody 2-17/2-30 compared to control antibodies. FIG.59G shows virus neutralization with the bispecific antibody 2-36/2-17compared to control antibodies.

FIG. 60 shows potencies of bispecific antibodies with 2-17 (NTD) as aparental antibody. The IC₅₀ of bispecific antibody 2-17/1-57 is 0.075μg/ml. The IC₉₀ of bispecific antibody 2-17/1-57 is 0.144 μg/ml. TheIC₅₀ of bispecific antibody 2-17/2-7 is 0.009 μg/ml. The IC₉₀ ofbispecific antibody 2-17/2-7 is 0.027 μg/ml. The IC₅₀ of bispecificantibody 2-17/2-15 is 0.005 μg/ml. The IC₉₀ of bispecific antibody2-17/2-15 is 0.087 μg/ml. The IC₅₀ of bispecific antibody 2-17/2-30 is0.065 μg/ml. The IC₉₀ of bispecific antibody 2-17/2-30 is μg/ml. TheIC₅₀ of bispecific antibody 2-17/4-20 is 0.029 μg/ml. The IC₉₀ ofbispecific antibody 2-17/4-20 is 0.164 μg/ml. The IC₅₀ of bispecificantibody 2-36/2-17 is 0.063 μg/ml. The IC₉₀ of bispecific antibody2-36/2-17 is 4.55 μg/ml.

FIGS. 61A-D show bispecific antibodies with 5-24 (NTD) as a parentalantibody. FIG. 61A shows virus neutralization with bispecific antibodies5-24/4-20, 5-24/1-57, 5-24/2-15, and 1-20/5-24. FIG. 61B shows virusneutralization with the bispecific antibody 5-24/2-compared to controlantibodies. FIG. 61C shows virus neutralization with the bispecificantibody 5-24/1-57 compared to control antibodies. FIG. 61D shows virusneutralization with the bispecific antibody 5-24/4-20 compared tocontrol antibodies.

FIG. 62 shows potencies of bispecific antibodies with 5-24 (NTD) as aparental antibody. The IC₅₀ of bispecific antibody 1-20/5-24 is 0.009μg/ml. The IC₉₀ of bispecific antibody 1-20/5-24 is 0.035 μg/ml. TheIC₅₀ of bispecific antibody 5-24/2-15 is 0.003 μg/ml. The IC₉₀ ofbispecific antibody 5-24/2-15 is 0.033 μg/ml. The IC₅₀ of bispecificantibody 5-24/1-57 is 0.004 μg/ml. The IC₉₀ of bispecific antibody5-24/1-57 is 0.045 μg/ml. The IC₅₀ of bispecific antibody 5-24/4-20 is0.062 μg/ml. The IC₉₀ of bispecific antibody 5-24/4-20 is μg/ml.

FIGS. 63A-D show bispecific antibodies with 2-36 (RBD) as a parentalantibody. FIG. 63A shows virus neutralization with bispecific antibodies2-36/1-68, 2-36/4-18, and 2-36/2-17. FIG. 63B shows virus neutralizationwith the bispecific antibody 2-36/2-17 compared to control antibodies.FIG. 63C shows virus neutralization with the bispecific antibody2-36/1-68 compared to control antibodies. FIG. 63D shows virusneutralization with the bispecific antibody 2-36/4-18 compared tocontrol antibodies.

FIG. 64 shows potencies of bispecific antibodies with 2-36 (RBD) as aparental antibody. The IC₅₀ of bispecific antibody 2-36/1-69 is 0.096μg/ml. The IC₉₀ of bispecific antibody 2-36/1-68 is 9.948 μg/ml. TheIC₅₀ of bispecific antibody 2-36/4-18 is 0.03 μg/ml. The IC₉₀ ofbispecific antibody 2-36/4-18 is 0.982 μg/ml. The IC₅₀ of bispecificantibody 2-36/2-17 is 0.063 μg/ml. The IC₉₀ of bispecific antibody2-36/2-17 is 4.55 μg/ml.

FIGS. 65A-C show bispecific antibodies with 2-30 (RBD) as a parentalantibody. FIG. 65A shows virus neutralization with bispecific antibodies2-30/4-18 and 2-30/1-68. FIG. 65B shows virus neutralization with thebispecific antibody 2-30/1-68 compared to control antibodies. FIG. 65Cshows virus neutralization with the bispecific antibody 2-30/4-18compared to control antibodies.

FIG. 66 shows potencies of bispecific antibodies with 2-30 (RBD) as aparental antibody. The IC₅₀ of bispecific antibody 2-30/4-18 is 0.026μg/ml. The IC₉₀ of bispecific antibody 2-30/4-18 is 0.096 μg/ml. TheIC₅₀ of bispecific antibody 2-30/1-68 is 0.008 μg/ml. The IC₉₀ ofbispecific antibody 2-30/1-68 is 0.036 μg/ml.

FIGS. 67A-D show comparative evaluations of bispecific antibody2-17/2-7. FIG. 67A shows the potency of the 2-17/2-7 bispecific antibodycompared to an antibody where one arm resembles the individual parentalcomponent of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 67Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 67C shows virus neutralizationwith the bispecific antibody 2-17/2-7 compared to a combination of theparental antibodies. FIG. 67D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody. The IC₅₀ of bispecific antibody2-17/2-7 is 0.005 μg/ml. The IC₉₀ of bispecific antibody 2-17/2-7 is0.02 μg/ml. The IC₅₀ of the combination of parental antibodies is 0.014μg/ml. The IC₉₀ of the combination of parental antibodies is 0.07 μg/ml.

FIGS. 68A-D show comparative evaluations of bispecific antibody1-20/4-18. FIG. 68A shows the potency of the 1-20/4-18 bispecificantibody compared to an antibody where one arm resembles the individualparental component of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 68Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 68C shows virus neutralizationwith the bispecific antibody 1-20/4-18 compared to a combination of theparental antibodies. FIG. 68D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody. The IC₅₀ of bispecific antibody1-20/4-18 is 0.016 μg/ml. The IC₉₀ of bispecific antibody 1-20/4-18 is0.076 μg/ml. The IC₅₀ of the combination of parental antibodies is 0.014μg/ml. The IC₉₀ of the combination of parental antibodies is 0.057μg/ml.

FIGS. 69A-D show comparative evaluations of bispecific antibody1-20/5-24. FIG. 69A shows the potency of the 1-20/5-24 bispecificantibody compared to an antibody where one arm resembles the individualparental component of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 69Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 69C shows virus neutralizationwith the bispecific antibody 1-20/5-24 compared to a combination of theparental antibodies. FIG. 69D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody. The IC₅₀ of bispecific antibody1-20/5-24 is 0.012 μg/ml. The IC₉₀ of bispecific antibody 1-20/5-24 is0.023 μg/ml. The IC₅₀ of the combination of parental antibodies is 0.004μg/ml. The IC₉₀ of the combination of parental antibodies is 0.016μg/ml.

FIGS. 70A-D show comparative evaluations of bispecific antibody2-17/4-20. FIG. 70A shows the potency of the 2-17/4-20 bispecificantibody to an antibody where one arm resembles the individual parentalcomponent of the bispecific antibody while the other arm is anirrelevant control. It also compares the potency of the bispecificantibody to the combination of the two single arm IgG controls. FIG. 70Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 70C shows virus neutralizationwith the bispecific antibody 2-17/4-20 compared to a combination of theparental antibodies. FIG. 70D shows potency of combination parentalmonoclonal antibodies tested each at half of the amount of thecorresponding bispecific antibody. The IC₅₀ of bispecific antibody2-17/4-20 is 0.042 μg/ml. The IC₉₀ of bispecific antibody 2-17/4-20 is0.097 μg/ml. The IC₅₀ of the combination of parental antibodies is 0.021μg/ml. The IC₉₀ of the combination of parental antibodies is 0.135μg/ml.

FIGS. 71A-B show in vitro potency of bispecific antibodies againstSARS-CoV-2 authentic virus, strain USA/WA1. FIG. 71A showsneutralization for ten bispecific antibodies with IC₉₀ concentrationsbetween 0.003 μg/ml and 0.023 μg/ml. FIG. 71B shows neutralization fornine bispecific antibodies with IC₉₀ concentrations between 0.025 μg/mland 0.046 μg/ml.

FIG. 72 shows in vitro potency of bispecific antibodies as indicated byrespective IC₅₀ and IC₉₀ concentrations.

FIGS. 73A-B show in vitro potency of bispecific antibodies showing IC₉₀and IC₅₀ concentrations. FIG. 73A shows in vitro potency of bispecificantibodies showing IC₉₀ and IC₅₀ concentrations relative to a 0.05 μg/mlthreshold. FIG. 73B shows in vitro potency of bispecific antibodiesshowing IC₉₀ and IC₅₀ concentrations relative to a 0.01 μg/ml threshold.FIGS. 73A and 73B are two separated “SORTED” data. In A, the data issorted by the top 20 bispecific antibody having the highest to lowestinhibition against 90% of the viruses (IC₉₀). In B, the data is sortedby the top 20 bispecific antibody having the highest to lowestinhibition against 50% of the viruses (IC₅₀).

FIGS. 74A-D show comparative evaluation of the bispecific antibody1-57/1-68. FIG. 74A shows virus neutralization with the bispecificantibody 1-57/1-68 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arm, wherein AbX is PGDM1400. FIG. 74B showsvirus neutralization with a combination of the parental antibodies andeach of the parental antibodies. FIG. 74C shows virus neutralizationwith the bispecific antibody 1-57/1-68 compared to a combination of theparental antibodies. FIG. 74D shows potency of the bispecific antibody1-57/1-68 and a mix of each parental monoclonal antibodies tested eachat half of the amount of the corresponding bispecific antibody. The IC₅₀of bispecific antibody 1-57/1-68 is 0.002 μg/ml. The IC₉₀ of bispecificantibody 1-57/1-68 is 0.005 μg/ml. The IC₅₀ of the combination ofparental antibodies is 0.006 μg/ml. The IC₉₀ of the combination ofparental antibodies is 0.02 μg/ml. The comparative data are from asingle experiment, while, the data in the summary table are averagedfrom multiple repeats.

FIGS. 75A-D show comparative evaluation of the bispecific antibody2-17/2-7. FIG. 75A shows virus neutralization with the bispecificantibody 2-17/2-7 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX and AbYare irrelevant control antibody arms, wherein AbX is PGDM1400 and AbY isA32. FIG. 75B shows virus neutralization with a combination of theparental antibodies and each of the parental antibodies. FIG. 75C showsvirus neutralization with the bispecific antibody 2-17/2-7 compared to acombination of the parental antibodies. FIG. 75D shows potency of thebispecific antibody 2-17/2-7 and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The IC₅₀ of bispecific antibody 2-17/2-7 is 0.005μg/ml. The IC₉₀ of bispecific antibody 2-17/2-7 is 0.02 μg/ml. The IC₅₀of the combination of parental antibodies is 0.014 μg/ml. The IC₉₀ ofthe combination of parental antibodies is 0.07 μg/ml. The comparativedata are from a single experiment, while, the data in the summary tableare averaged from multiple repeats.

FIGS. 76A-D show comparative evaluation of the bispecific antibody1-20/4-18. FIG. 76A shows virus neutralization with the bispecificantibody 1-20/4-18 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX and AbYare irrelevant control antibody arms, wherein AbX is PGDM1400 and AbY isA32. FIG. 76B shows virus neutralization with a combination of theparental antibodies and each of the parental antibodies. FIG. 76C showsvirus neutralization with the bispecific antibody 1-20/4-18 compared toa combination of the parental antibodies. FIG. 76D shows potency of thebispecific antibody 1-20/4-18 and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The IC₅₀ of bispecific antibody 1-20/4-18 is 0.016μg/ml. The IC₉₀ of bispecific antibody 1-20/4-18 is 0.077 μg/ml. TheIC₅₀ of the combination of parental antibodies is 0.014 μg/ml. The IC₉₀of the combination of the parental antibodies is 0.057 μg/ml. Thecomparative data are from a single experiment, while, the data in thesummary table are averaged from multiple repeats.

FIGS. 77A-D show comparative evaluation of the bispecific antibody1-20/5-24. FIG. 77A shows virus neutralization with the bispecificantibody 1-20/5-24 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX and AbYare irrelevant control antibody arms, wherein AbX is PGDM1400 and AbY isA32. FIG. 77B shows virus neutralization with a combination of theparental antibodies and each of the parental antibodies. FIG. 77C showsvirus neutralization with the bispecific antibody 1-20/5-24 compared toa combination of the parental antibodies. FIG. 77D shows potency of thebispecific antibody 1-20/5-24 and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The IC₅₀ of bispecific antibody 1-20/5-24 is 0.012μg/ml. The IC₉₀ of bispecific antibody 1-20/5-24 is 0.023 μg/ml. TheIC₅₀ of the combination of parental antibodies is 0.004 μg/ml. The IC₉₀of the combination of parental antibodies is 0.016 μg/ml. Thecomparative data are from a single experiment, while, the data in thesummary table are averaged from multiple repeats.

FIGS. 78A-D show comparative evaluation of the bispecific antibody2-30/1-68. FIG. 78A shows virus neutralization with the bispecificantibody 2-30/1-68 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arms, wherein AbX is PGDM1400. FIG. 78Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 78C shows virus neutralizationwith the bispecific antibody 2-30/1-68 compared to a combination of theparental antibodies. FIG. 78D shows potency of the bispecific antibody2-30/1-68 and a mix of each parental monoclonal antibodies tested eachat half of the amount of the corresponding bispecific antibody. The IC₅₀of bispecific antibody 2-30/1-68 is 0.009 μg/ml. The IC₉₀ of bispecificantibody 2-30/1-68 is 0.034 μg/ml. The IC₅₀ of the combination ofparental antibodies is 0.009 μg/ml. The IC₉₀ of the combination ofparental antibodies is 0.086 μg/ml. The comparative data are from asingle experiment, while, the data in the summary table are averagedfrom multiple repeats.

FIGS. 79A-D show comparative evaluation of the bispecific antibody2-7/4-8 (39/51). FIG. 79A shows virus neutralization with the bispecificantibody 2-7/4-8 (39/51) compared to two control bispecific antibodies,each comprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arms, wherein AbX is PGDM1400. FIG. 79Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 79C shows virus neutralizationwith the bispecific antibody 2-7/4-8 (39/51) compared to a combinationof the parental antibodies. FIG. 79D shows potency of the bispecificantibody 2-7/4-8 (39/51) and a mix of each parental monoclonalantibodies tested each at half of the amount of the correspondingbispecific antibody. The IC₅₀ of bispecific antibody 2-7/4-8(39/51) is0.0008 μg/ml. The IC₉₀ of bispecific antibody 2-7/4-8(39/51) is 0.002μg/ml. The comparative data are from a single experiment, while, thedata in the summary table are averaged from multiple repeats.

FIGS. 80A-D show comparative evaluation of the bispecific antibody1-57/1-87. FIG. 80A shows virus neutralization with the bispecificantibody 1-57/1-87 compared to two control bispecific antibodies, eachcomprising a parental antibody arm and a control antibody arm, andcompared to a mix of the two control bispecific antibodies. AbX is anirrelevant control antibody arms, wherein AbX is PGDM1400. FIG. 80Bshows virus neutralization with a combination of the parental antibodiesand each of the parental antibodies. FIG. 80C shows virus neutralizationwith the bispecific antibody 1-57/1-87 compared to a combination of theparental antibodies. FIG. 80D shows potency of the bispecific antibody1-57/1-87 and a mix of each parental monoclonal antibodies tested eachat half of the amount of the corresponding bispecific antibody. The IC₅₀of bispecific antibody 1-57/1-87 is 0.0012 μg/ml. The IC₉₀ of bispecificantibody 1-57/1-87 is 0.002 μg/ml. The IC₅₀ of the combination ofparental antibodies is 0.0012 μg/ml. The IC₉₀ of the combination ofparental antibodies is 0.010 μg/ml. The comparative data are from asingle experiment, while, the data in the summary table are averagedfrom multiple repeats.

FIG. 81 shows potency of additional bispecific antibodies.

Example 16—Bispecific Against SARS-CoV-2 Variants

FIGS. 82A-B show neutralizing activities of engineered bispecificantibodies. FIG. 82A shows neutralizing activities against wild-typevirus (WA1) at various antibody concentrations for bispecific antibodies2-17/2-7, 1-57/5-7, 5-7/1-57, 2-7/5-7, 5-7/2-7. FIG. 82B shows antibodypotency (IC₅₀ and IC₉₀) against wild-type virus (WA1) for bispecificantibodies 2-17/2-7 (control), 1-57/5-7, 5-7/1-57, 2-7/5-7, 5-7/2-7. TheIC₅₀ of bispecific antibody 2-17/2-7 is 0.005˜0.008 μg/ml. The IC₉₀ ofbispecific antibody 2-17/2-7 is 0.025˜0.055 μg/ml. The IC₅₀ ofbispecific antibody 1-57/5-7 is 0.005 μg/ml. The IC₉₀ of bispecificantibody 1-57/5-7 is 0.037 μg/ml. The IC₅₀ of bispecific antibody5-7/1-57 is 0.006 μg/ml. The IC₉₀ of bispecific antibody 5-7/1-57 is0.054 μg/ml. The IC₅₀ of bispecific antibody 2-7/5-7 is 0.005 μg/ml. TheIC₉₀ of bispecific antibody 2-7/5-7 is 0.020 μg/ml. The IC₅₀ ofbispecific antibody 5-7/2-7 is 0.007 μg/ml. The IC₉₀ of bispecificantibody 5-7/2-7 is 0.049 μg/ml.

FIGS. 83A-B show 2-7/5-7 bispecific antibody and parental antibodiesactivities. FIG. 83A shows neutralizing activities against wild-typevirus (WA1) at various antibody concentrations for bispecific antibody2-7/5-7, parental antibodies 2-7, 5-7, and a combination of 2-7 and 5-7parental antibodies. FIG. 83B shows IC₅₀ concentrations for bispecificantibody 2-7/5-7, parental antibodies 2-7, 5-7, and a combination of 2-7and 5-7 parental antibodies. The IC₅₀ of parental antibody 2-7 is 0.009μg/ml. The IC₅₀ of parental antibody 5-7 is 0.044 μg/ml.

The IC₅₀ of bispecific antibody 2-7/5-7 is 0.002 μg/ml. The IC₅₀ of thecombination of parental antibodies 2-7 and 5-7 is 0.020 μg/ml.

FIGS. 84A-B show activities of bispecific antibody 2-7/5-7 againstSARS-CoV-2 wild-type (WA1) and variant strains B1.1.7, B1.526, B1351,and P.1. FIG. 84A shows neutralization activity of bispecific antibody2-7/5-7 against various SARS-CoV-2 strains at different antibodyconcentrations. The SARS-CoV-2 strains are WA1, B1.1.7, B1.351, B1.526,and P.1. FIG. 84B shows IC₅₀ and IC₉₀ concentrations for bispecificantibody 2-7/5-7 against various SARS-CoV-2 strains. The IC₅₀ for thebispecific antibody 2-7/5-7 against WA1 (wild-type strain) is 0.002μg/ml. The IC₉₀ for the bispecific antibody 2-7/5-7 against WA1(wild-type strain) is 0.019 μg/ml. The IC₅₀ for the bispecific antibody2-7/5-7 against B1.1.7 is 0.002 μg/ml. The IC₉₀ for the bispecificantibody 2-7/5-7 against B1.1.7 is 0.011 μg/ml. The IC₅₀ for thebispecific antibody 2-7/5-7 against B1.526 is 0.002 μg/ml. The IC₉₀ forthe bispecific antibody 2-7/5-7 against B1.526 is 0.01 μg/ml. The IC₅₀for the bispecific antibody 2-7/5-7 against B1.351 is 0.025 μg/ml. TheIC₉₀ for the bispecific antibody 2-7/5-7 against B1.351 is 0.156 μg/ml.The IC₅₀ for the bispecific antibody 2-7/5-7 against P.1 is 0.013 μg/ml.The IC₉₀ for the bispecific antibody 2-7/5-7 against P.1 is 0.188 μg/ml.

Example 17—Bispecific 2-7/5-7 Antibody

FIGS. 85A-D show neutralization of pseudoviruses having mutationsassociated with SARS-CoV-2 variants with the bispecific 2-7/5-7antibody. FIG. 85A shows antibody neutralization curves againstcirculating SARS-CoV-2 virus variants. FIG. 85B shows antibody potencyagainst circulating SARS-CoV-2 virus variants. FIG. 85C shows antibodyneutralization curves against SARS-CoV-2 variants with high frequencymutations. FIG. shows antibody potency against SARS-CoV-2 variants withhigh frequency mutations.

FIGS. 86A-F show neutralization of pseudoviruses with SARS-CoV-2mutations corresponding to “variants of concern” using the bispecificantibody 2-7/5-7. FIG. 86A shows antibody neutralization curves againstB.1.1.7 (UK virus variant) with NTD mutations. FIG. 86B shows antibodypotency against B.1.1.7 (UK virus variant) with NTD mutations. FIG. 86Cshows antibody neutralization curves against B.1.352 (SA) virus variantwith NTD mutations. FIG. 86D shows antibody potency against B.1.352 (SA)virus variant with NTD mutations. FIG. 86E shows antibody neutralizationcurves against P.1 (BZ) virus variant with NTD mutations. FIG. 86F showsantibody potency against P.1 (BZ) virus variant with NTD mutations.

FIGS. 87A-F show neutralization of pseudoviruses with SARS-CoV-2mutations corresponding to “variants of interest” using the bispecificantibody 2-7/5-7. FIG. 87A shows antibody neutralization curves againstB.1.427 (CA) virus variant with NTD mutations. FIG. 87B shows antibodypotency against B.1.427 (CA) virus variant with NTD mutations. FIG. 87Cshows antibody neutralization curves against B.1.526 (NY) variant withNTD mutations. FIG. 87D shows antibody potency against B.1.526 (NY)variant with NTD mutations. FIG. 87E show antibody neuralization curvesagainst NJ variant with NTD mutations. FIG. 87F show antibody potencyagainst NJ variant with NTD mutations.

FIG. 88 shows summary of bispecific antibody 2-7/5-7 activity againstvariants. 1050 is shown in circles. 1C90 is shown in squares.

FIGS. 89A-C shows neutralization activity of bispecific antibody 2-7/5-7and parental 2-7 and 5-7 monoclonal antibodies against SARS-CoV-2variants (live viruses). FIG. 89A shows the neutralization curve forbispecific antibody 2-7/5-7. FIG. 89B shows the neutralization curve forparental antibody 2-7. FIG. 89C shows the neutralization curve forparental antibody 5-7.

1.-172. (canceled)
 173. A synthesized monoclonal antibody, or afunctional fragment thereof, comprising a heavy chain having a variabledomain and a constant domain and a light chain having a variable domainand a constant domain, wherein the antibody binds an antigen on acoronavirus particle.
 174. The antibody of claim 173, wherein the heavychain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO: 1 and the light chainvariable domain comprises a polypeptide sequence which is at least 60%,62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%, 95%,97%, 98%, 99% identical to SEQ ID NO:
 2. 175. The antibody of claim 173,wherein the heavy chain variable domain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23 and thelight chain variable domain comprises a polypeptide sequence which is atleast 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%,92%, 95%, 97%, 98%, 99% identical to SEQ ID NO:
 24. 176. The antibody ofclaim 173, wherein the heavy chain variable domain comprises SEQ ID NO:1 and the light chain variable domain comprises SEQ ID NO:
 2. 177. Theantibody of claim 173, wherein the heavy chain variable domain comprisesSEQ ID NO: 23 and the light chain variable domain comprises SEQ ID NO:24.
 178. The antibody of claim 173, wherein the heavy chain variabledomain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 1 andthe light chain variable domain comprises the CDR1, CDR2, and CDR3regions of SEQ ID NO:
 2. 179. The antibody of claim 173, wherein theheavy chain variable domain comprises the CDR1, CDR2, and CDR3 regionsof SEQ ID NO: 23 and the light chain variable domain comprises the CDR1,CDR2, and CDR3 regions of SEQ ID NO:
 24. 180. The antibody of claim 173,wherein the antibody neutralizes a coronavirus.
 181. The antibody ofclaim 180, wherein the coronavirus is a SARS-CoV-2 wild type virus,SARS-CoV-2 WA1 variant, SARS-CoV-2 B.1.1.7 variant, SARS-CoV-2 B1.526variant, SARS-CoV-2 B1.351 variant, SARS-CoV-2 P1 variant, SARS-CoV-2B1.352 variant, or SARS-CoV-2 B.1.427 variant.
 182. The antibody ofclaim 173, wherein the antigen comprises at least a portion of areceptor binding domain (RBD) of a spike protein or at least a portionof a N-Terminal domain (NTD) of a spike protein.
 183. A method oftreating or preventing a COVID-19 infection in a subject in needthereof, the method comprising administering to the subject atherapeutically effective amount of a synthesized monoclonal antibody,or a functional fragment thereof, comprising a heavy chain having avariable domain and a constant domain and a light chain having avariable domain and a constant domain, wherein the antibody binds anantigen on a coronavirus particle.
 184. The method of claim 183, whereinthe heavy chain variable domain comprises a polypeptide sequence whichis at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%,90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 1 and the lightchain variable domain comprises a polypeptide sequence which is at least60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%, 87%, 90%, 92%,95%, 97%, 98%, 99% identical to SEQ ID NO:
 2. 185. The method of claim183, wherein the heavy chain variable domain comprises a polypeptidesequence which is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%,82%, 85%, 87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO: 23and the light chain variable domain comprises a polypeptide sequencewhich is at least 60%, 62%, 65%, 67%, 70%, 72%, 75%, 77%, 80%, 82%, 85%,87%, 90%, 92%, 95%, 97%, 98%, 99% identical to SEQ ID NO:
 24. 186. Themethod of claim 183, wherein the heavy chain variable domain comprisesSEQ ID NO: 1 and the light chain variable domain comprises SEQ ID NO: 2.187. The method of claim 183, wherein the heavy chain variable domaincomprises SEQ ID NO: 23 and the light chain variable domain comprisesSEQ ID NO:
 24. 188. The method of claim 183, wherein the heavy chainvariable domain comprises the CDR1, CDR2, and CDR3 regions of SEQ ID NO:1 and the light chain variable domain comprises the CDR1, CDR2, and CDR3regions of SEQ ID NO:
 2. 189. The method of claim 183, wherein the heavychain variable domain comprises the CDR1, CDR2, and CDR3 regions of SEQID NO: 23 and the light chain variable domain comprises the CDR1, CDR2,and CDR3 regions of SEQ ID NO:
 24. 190. The method of claim 183, whereinthe antibody neutralizes a coronavirus.
 191. The method of claim 190,wherein the coronavirus is a SARS-CoV-2 wild type virus, SARS-CoV-2 WA1variant, SARS-CoV-2 B.1.1.7 variant, SARS-CoV-2 B1.526 variant,SARS-CoV-2 B1.351 variant, SARS-CoV-2 P1 variant, SARS-CoV-2 B1.352variant, or SARS-CoV-2 B.1.427 variant.
 192. The method of claim 183,wherein the antigen comprises at least a portion of a receptor bindingdomain (RBD) of a spike protein or at least a portion of a N-Terminaldomain (NTD) of a spike protein.